lipofilling and oncoplastic breast surgery : oncologic … · mda-mb-436 mda-mb-436 cd34+ wat cells...

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LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic safety JY Petit IEO Milan December 13-15, 2012 29 th Annual New York Controversies, Problems & Techniques in Surgery SYMPOSIUM COURSE DIRECTORS Robert Michler, MD; Steven Libutti, MD; Peter Shamamian, MD Controversies, Problems & Techniques in Surgery NO DISCLOSURE This presentation is the intellectual property of the presenter. Contact him for permission to reprint and/or to distribute

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Page 1: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

LIPOFILLING AND

ONCOPLASTIC BREAST

SURGERY oncologic safety

JY Petit IEO Milan

December 13-15 2012

29th Annual New York

Controversies Problems amp

Techniques in Surgery SYMPOSIUM COURSE DIRECTORS

Robert Michler MD Steven Libutti MD Peter Shamamian MD

Controversies Problems amp Techniques in Surgery

NO DISCLOSURE This presentation is the intellectual

property of the presenter Contact him for

permission to reprint andor to distribute

Immediate remodelling after tumourectomy

Indications

Conservative surgery

40g AL

Conservative surgery

60 g AL

Conservative surgery

50 g AL

Implant BR 40g AL

Implant reconstruction

50 g AL

175 m 46 kil

55 g left breast

Breast volume augmentation

Coleman technique

scar

improvement

Immediate Pre-op Intraop after debridement

25 Days Post Op 41 Days Post Op

Intra-op after Cell Tx

14 Days Post Op

90 y old women 40 years after abdominal radiation therapy

and non healing sacral pressure sore Dr Sadanori Akita

90 cells to circular area around sore

10 cells to sore itself

145 days

1994 Osteosarcoma tt

2006 lipofilling

Clinical

results

LR of osteosarcoma

13 y after TT

18 mths after lipofilling

Local recurrence

Kotaro Yoshimura MD

SAFETY OF LIPOFILLING

IN BREAST CANCER PATIENTS

From the lab

to clinical results

FBERTOLINI

IMARTIN PADURA

IEO Milan

NOS DISCLOSURE

Review

ldquoAdipose tissue cells lipotransfer and cancer

A challenge for scientists oncologists and

surgeonsrdquo Francesco Bertolinia

Abdominal or thigh Human WAT

gt150 samples

Immunomagnetic separation

Enzymatic digestion

155 Samples FROM LIPOTRANSFER HAVE BEEN PURIFIED

F BERTOLINIrsquoS LAB

Purified CD34+ WAT-derived cells

COLEMAN TECHNIQUE

Stromal vascular fraction

NSG Females 8 weeks old

cells suspension injected in the fourth mammary fad pad directly though the nipple

Tumors are detectable at day 7 raise 800-1000 mm3 in 35-40 days

106 breast cancer cells 106 breast cancer cells + 2x105 WAT cells

cell suspension in matrigel +blu dye

Transplant of a human breast cell line on the mammary gland of a imunodeficient mouse to develop a breast cancer mouse model

MDA-MB-436 MDA-MB-436 CD34+ WAT cells

0

500

1000

1500

2000

2500

0 29 62 76T

um

or

vo

lum

e (

mm

3)

Days

CD34+

Unfractionated

Control

CD34+ no tumor

Breast cell line 1 (MDA-MB-436)

0

50

100

150

200

250

0 36 63 70 88 95

Tu

mo

r vo

lum

e (

mm

3)

Days

Control

Breast cell line 2 (HCC1937)

Adipose derived CD34+ cells promote breast tumor growth

in vivo

Tumors were bigger when co-transplanted

with adipose cells

hellipand this was true with two different breast cell lines

mastectomy primary tumor

axillary lympho

node metastases

lung

metastases

Injection of CD34+WAT-derived cells increases lung metastases

WAT cells

0

5

10

15

20

25

30

Lung Metastases

Controls

CD34- injected

CD34+ injected

2012

9269 with oncologic FU

Only 29 with a control group (Rigotti - Petit)

Only 1 with a cohort study group (Petit)

Eur J Surg Oncol 2012 May38(5)382-9 Epub 2012 Mar 15

Prospective trial of adipose-derived

regenerative cell (ADRC)-enriched fat grafting

for partial mastectomy defects the RESTORE-

2 trial Peacuterez-Cano R Vranckx JJ Lasso JM Calabrese C Merck B Milstein AM

Sassoon E Delay E Weiler-Mithoff EM

No local recurrence

No control group

Very short follow up

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 2: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

Immediate remodelling after tumourectomy

Indications

Conservative surgery

40g AL

Conservative surgery

60 g AL

Conservative surgery

50 g AL

Implant BR 40g AL

Implant reconstruction

50 g AL

175 m 46 kil

55 g left breast

Breast volume augmentation

Coleman technique

scar

improvement

Immediate Pre-op Intraop after debridement

25 Days Post Op 41 Days Post Op

Intra-op after Cell Tx

14 Days Post Op

90 y old women 40 years after abdominal radiation therapy

and non healing sacral pressure sore Dr Sadanori Akita

90 cells to circular area around sore

10 cells to sore itself

145 days

1994 Osteosarcoma tt

2006 lipofilling

Clinical

results

LR of osteosarcoma

13 y after TT

18 mths after lipofilling

Local recurrence

Kotaro Yoshimura MD

SAFETY OF LIPOFILLING

IN BREAST CANCER PATIENTS

From the lab

to clinical results

FBERTOLINI

IMARTIN PADURA

IEO Milan

NOS DISCLOSURE

Review

ldquoAdipose tissue cells lipotransfer and cancer

A challenge for scientists oncologists and

surgeonsrdquo Francesco Bertolinia

Abdominal or thigh Human WAT

gt150 samples

Immunomagnetic separation

Enzymatic digestion

155 Samples FROM LIPOTRANSFER HAVE BEEN PURIFIED

F BERTOLINIrsquoS LAB

Purified CD34+ WAT-derived cells

COLEMAN TECHNIQUE

Stromal vascular fraction

NSG Females 8 weeks old

cells suspension injected in the fourth mammary fad pad directly though the nipple

Tumors are detectable at day 7 raise 800-1000 mm3 in 35-40 days

106 breast cancer cells 106 breast cancer cells + 2x105 WAT cells

cell suspension in matrigel +blu dye

Transplant of a human breast cell line on the mammary gland of a imunodeficient mouse to develop a breast cancer mouse model

MDA-MB-436 MDA-MB-436 CD34+ WAT cells

0

500

1000

1500

2000

2500

0 29 62 76T

um

or

vo

lum

e (

mm

3)

Days

CD34+

Unfractionated

Control

CD34+ no tumor

Breast cell line 1 (MDA-MB-436)

0

50

100

150

200

250

0 36 63 70 88 95

Tu

mo

r vo

lum

e (

mm

3)

Days

Control

Breast cell line 2 (HCC1937)

Adipose derived CD34+ cells promote breast tumor growth

in vivo

Tumors were bigger when co-transplanted

with adipose cells

hellipand this was true with two different breast cell lines

mastectomy primary tumor

axillary lympho

node metastases

lung

metastases

Injection of CD34+WAT-derived cells increases lung metastases

WAT cells

0

5

10

15

20

25

30

Lung Metastases

Controls

CD34- injected

CD34+ injected

2012

9269 with oncologic FU

Only 29 with a control group (Rigotti - Petit)

Only 1 with a cohort study group (Petit)

Eur J Surg Oncol 2012 May38(5)382-9 Epub 2012 Mar 15

Prospective trial of adipose-derived

regenerative cell (ADRC)-enriched fat grafting

for partial mastectomy defects the RESTORE-

2 trial Peacuterez-Cano R Vranckx JJ Lasso JM Calabrese C Merck B Milstein AM

Sassoon E Delay E Weiler-Mithoff EM

No local recurrence

No control group

Very short follow up

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 3: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

Indications

Conservative surgery

40g AL

Conservative surgery

60 g AL

Conservative surgery

50 g AL

Implant BR 40g AL

Implant reconstruction

50 g AL

175 m 46 kil

55 g left breast

Breast volume augmentation

Coleman technique

scar

improvement

Immediate Pre-op Intraop after debridement

25 Days Post Op 41 Days Post Op

Intra-op after Cell Tx

14 Days Post Op

90 y old women 40 years after abdominal radiation therapy

and non healing sacral pressure sore Dr Sadanori Akita

90 cells to circular area around sore

10 cells to sore itself

145 days

1994 Osteosarcoma tt

2006 lipofilling

Clinical

results

LR of osteosarcoma

13 y after TT

18 mths after lipofilling

Local recurrence

Kotaro Yoshimura MD

SAFETY OF LIPOFILLING

IN BREAST CANCER PATIENTS

From the lab

to clinical results

FBERTOLINI

IMARTIN PADURA

IEO Milan

NOS DISCLOSURE

Review

ldquoAdipose tissue cells lipotransfer and cancer

A challenge for scientists oncologists and

surgeonsrdquo Francesco Bertolinia

Abdominal or thigh Human WAT

gt150 samples

Immunomagnetic separation

Enzymatic digestion

155 Samples FROM LIPOTRANSFER HAVE BEEN PURIFIED

F BERTOLINIrsquoS LAB

Purified CD34+ WAT-derived cells

COLEMAN TECHNIQUE

Stromal vascular fraction

NSG Females 8 weeks old

cells suspension injected in the fourth mammary fad pad directly though the nipple

Tumors are detectable at day 7 raise 800-1000 mm3 in 35-40 days

106 breast cancer cells 106 breast cancer cells + 2x105 WAT cells

cell suspension in matrigel +blu dye

Transplant of a human breast cell line on the mammary gland of a imunodeficient mouse to develop a breast cancer mouse model

MDA-MB-436 MDA-MB-436 CD34+ WAT cells

0

500

1000

1500

2000

2500

0 29 62 76T

um

or

vo

lum

e (

mm

3)

Days

CD34+

Unfractionated

Control

CD34+ no tumor

Breast cell line 1 (MDA-MB-436)

0

50

100

150

200

250

0 36 63 70 88 95

Tu

mo

r vo

lum

e (

mm

3)

Days

Control

Breast cell line 2 (HCC1937)

Adipose derived CD34+ cells promote breast tumor growth

in vivo

Tumors were bigger when co-transplanted

with adipose cells

hellipand this was true with two different breast cell lines

mastectomy primary tumor

axillary lympho

node metastases

lung

metastases

Injection of CD34+WAT-derived cells increases lung metastases

WAT cells

0

5

10

15

20

25

30

Lung Metastases

Controls

CD34- injected

CD34+ injected

2012

9269 with oncologic FU

Only 29 with a control group (Rigotti - Petit)

Only 1 with a cohort study group (Petit)

Eur J Surg Oncol 2012 May38(5)382-9 Epub 2012 Mar 15

Prospective trial of adipose-derived

regenerative cell (ADRC)-enriched fat grafting

for partial mastectomy defects the RESTORE-

2 trial Peacuterez-Cano R Vranckx JJ Lasso JM Calabrese C Merck B Milstein AM

Sassoon E Delay E Weiler-Mithoff EM

No local recurrence

No control group

Very short follow up

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 4: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

Conservative surgery

40g AL

Conservative surgery

60 g AL

Conservative surgery

50 g AL

Implant BR 40g AL

Implant reconstruction

50 g AL

175 m 46 kil

55 g left breast

Breast volume augmentation

Coleman technique

scar

improvement

Immediate Pre-op Intraop after debridement

25 Days Post Op 41 Days Post Op

Intra-op after Cell Tx

14 Days Post Op

90 y old women 40 years after abdominal radiation therapy

and non healing sacral pressure sore Dr Sadanori Akita

90 cells to circular area around sore

10 cells to sore itself

145 days

1994 Osteosarcoma tt

2006 lipofilling

Clinical

results

LR of osteosarcoma

13 y after TT

18 mths after lipofilling

Local recurrence

Kotaro Yoshimura MD

SAFETY OF LIPOFILLING

IN BREAST CANCER PATIENTS

From the lab

to clinical results

FBERTOLINI

IMARTIN PADURA

IEO Milan

NOS DISCLOSURE

Review

ldquoAdipose tissue cells lipotransfer and cancer

A challenge for scientists oncologists and

surgeonsrdquo Francesco Bertolinia

Abdominal or thigh Human WAT

gt150 samples

Immunomagnetic separation

Enzymatic digestion

155 Samples FROM LIPOTRANSFER HAVE BEEN PURIFIED

F BERTOLINIrsquoS LAB

Purified CD34+ WAT-derived cells

COLEMAN TECHNIQUE

Stromal vascular fraction

NSG Females 8 weeks old

cells suspension injected in the fourth mammary fad pad directly though the nipple

Tumors are detectable at day 7 raise 800-1000 mm3 in 35-40 days

106 breast cancer cells 106 breast cancer cells + 2x105 WAT cells

cell suspension in matrigel +blu dye

Transplant of a human breast cell line on the mammary gland of a imunodeficient mouse to develop a breast cancer mouse model

MDA-MB-436 MDA-MB-436 CD34+ WAT cells

0

500

1000

1500

2000

2500

0 29 62 76T

um

or

vo

lum

e (

mm

3)

Days

CD34+

Unfractionated

Control

CD34+ no tumor

Breast cell line 1 (MDA-MB-436)

0

50

100

150

200

250

0 36 63 70 88 95

Tu

mo

r vo

lum

e (

mm

3)

Days

Control

Breast cell line 2 (HCC1937)

Adipose derived CD34+ cells promote breast tumor growth

in vivo

Tumors were bigger when co-transplanted

with adipose cells

hellipand this was true with two different breast cell lines

mastectomy primary tumor

axillary lympho

node metastases

lung

metastases

Injection of CD34+WAT-derived cells increases lung metastases

WAT cells

0

5

10

15

20

25

30

Lung Metastases

Controls

CD34- injected

CD34+ injected

2012

9269 with oncologic FU

Only 29 with a control group (Rigotti - Petit)

Only 1 with a cohort study group (Petit)

Eur J Surg Oncol 2012 May38(5)382-9 Epub 2012 Mar 15

Prospective trial of adipose-derived

regenerative cell (ADRC)-enriched fat grafting

for partial mastectomy defects the RESTORE-

2 trial Peacuterez-Cano R Vranckx JJ Lasso JM Calabrese C Merck B Milstein AM

Sassoon E Delay E Weiler-Mithoff EM

No local recurrence

No control group

Very short follow up

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 5: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

Conservative surgery

60 g AL

Conservative surgery

50 g AL

Implant BR 40g AL

Implant reconstruction

50 g AL

175 m 46 kil

55 g left breast

Breast volume augmentation

Coleman technique

scar

improvement

Immediate Pre-op Intraop after debridement

25 Days Post Op 41 Days Post Op

Intra-op after Cell Tx

14 Days Post Op

90 y old women 40 years after abdominal radiation therapy

and non healing sacral pressure sore Dr Sadanori Akita

90 cells to circular area around sore

10 cells to sore itself

145 days

1994 Osteosarcoma tt

2006 lipofilling

Clinical

results

LR of osteosarcoma

13 y after TT

18 mths after lipofilling

Local recurrence

Kotaro Yoshimura MD

SAFETY OF LIPOFILLING

IN BREAST CANCER PATIENTS

From the lab

to clinical results

FBERTOLINI

IMARTIN PADURA

IEO Milan

NOS DISCLOSURE

Review

ldquoAdipose tissue cells lipotransfer and cancer

A challenge for scientists oncologists and

surgeonsrdquo Francesco Bertolinia

Abdominal or thigh Human WAT

gt150 samples

Immunomagnetic separation

Enzymatic digestion

155 Samples FROM LIPOTRANSFER HAVE BEEN PURIFIED

F BERTOLINIrsquoS LAB

Purified CD34+ WAT-derived cells

COLEMAN TECHNIQUE

Stromal vascular fraction

NSG Females 8 weeks old

cells suspension injected in the fourth mammary fad pad directly though the nipple

Tumors are detectable at day 7 raise 800-1000 mm3 in 35-40 days

106 breast cancer cells 106 breast cancer cells + 2x105 WAT cells

cell suspension in matrigel +blu dye

Transplant of a human breast cell line on the mammary gland of a imunodeficient mouse to develop a breast cancer mouse model

MDA-MB-436 MDA-MB-436 CD34+ WAT cells

0

500

1000

1500

2000

2500

0 29 62 76T

um

or

vo

lum

e (

mm

3)

Days

CD34+

Unfractionated

Control

CD34+ no tumor

Breast cell line 1 (MDA-MB-436)

0

50

100

150

200

250

0 36 63 70 88 95

Tu

mo

r vo

lum

e (

mm

3)

Days

Control

Breast cell line 2 (HCC1937)

Adipose derived CD34+ cells promote breast tumor growth

in vivo

Tumors were bigger when co-transplanted

with adipose cells

hellipand this was true with two different breast cell lines

mastectomy primary tumor

axillary lympho

node metastases

lung

metastases

Injection of CD34+WAT-derived cells increases lung metastases

WAT cells

0

5

10

15

20

25

30

Lung Metastases

Controls

CD34- injected

CD34+ injected

2012

9269 with oncologic FU

Only 29 with a control group (Rigotti - Petit)

Only 1 with a cohort study group (Petit)

Eur J Surg Oncol 2012 May38(5)382-9 Epub 2012 Mar 15

Prospective trial of adipose-derived

regenerative cell (ADRC)-enriched fat grafting

for partial mastectomy defects the RESTORE-

2 trial Peacuterez-Cano R Vranckx JJ Lasso JM Calabrese C Merck B Milstein AM

Sassoon E Delay E Weiler-Mithoff EM

No local recurrence

No control group

Very short follow up

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 6: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

Conservative surgery

50 g AL

Implant BR 40g AL

Implant reconstruction

50 g AL

175 m 46 kil

55 g left breast

Breast volume augmentation

Coleman technique

scar

improvement

Immediate Pre-op Intraop after debridement

25 Days Post Op 41 Days Post Op

Intra-op after Cell Tx

14 Days Post Op

90 y old women 40 years after abdominal radiation therapy

and non healing sacral pressure sore Dr Sadanori Akita

90 cells to circular area around sore

10 cells to sore itself

145 days

1994 Osteosarcoma tt

2006 lipofilling

Clinical

results

LR of osteosarcoma

13 y after TT

18 mths after lipofilling

Local recurrence

Kotaro Yoshimura MD

SAFETY OF LIPOFILLING

IN BREAST CANCER PATIENTS

From the lab

to clinical results

FBERTOLINI

IMARTIN PADURA

IEO Milan

NOS DISCLOSURE

Review

ldquoAdipose tissue cells lipotransfer and cancer

A challenge for scientists oncologists and

surgeonsrdquo Francesco Bertolinia

Abdominal or thigh Human WAT

gt150 samples

Immunomagnetic separation

Enzymatic digestion

155 Samples FROM LIPOTRANSFER HAVE BEEN PURIFIED

F BERTOLINIrsquoS LAB

Purified CD34+ WAT-derived cells

COLEMAN TECHNIQUE

Stromal vascular fraction

NSG Females 8 weeks old

cells suspension injected in the fourth mammary fad pad directly though the nipple

Tumors are detectable at day 7 raise 800-1000 mm3 in 35-40 days

106 breast cancer cells 106 breast cancer cells + 2x105 WAT cells

cell suspension in matrigel +blu dye

Transplant of a human breast cell line on the mammary gland of a imunodeficient mouse to develop a breast cancer mouse model

MDA-MB-436 MDA-MB-436 CD34+ WAT cells

0

500

1000

1500

2000

2500

0 29 62 76T

um

or

vo

lum

e (

mm

3)

Days

CD34+

Unfractionated

Control

CD34+ no tumor

Breast cell line 1 (MDA-MB-436)

0

50

100

150

200

250

0 36 63 70 88 95

Tu

mo

r vo

lum

e (

mm

3)

Days

Control

Breast cell line 2 (HCC1937)

Adipose derived CD34+ cells promote breast tumor growth

in vivo

Tumors were bigger when co-transplanted

with adipose cells

hellipand this was true with two different breast cell lines

mastectomy primary tumor

axillary lympho

node metastases

lung

metastases

Injection of CD34+WAT-derived cells increases lung metastases

WAT cells

0

5

10

15

20

25

30

Lung Metastases

Controls

CD34- injected

CD34+ injected

2012

9269 with oncologic FU

Only 29 with a control group (Rigotti - Petit)

Only 1 with a cohort study group (Petit)

Eur J Surg Oncol 2012 May38(5)382-9 Epub 2012 Mar 15

Prospective trial of adipose-derived

regenerative cell (ADRC)-enriched fat grafting

for partial mastectomy defects the RESTORE-

2 trial Peacuterez-Cano R Vranckx JJ Lasso JM Calabrese C Merck B Milstein AM

Sassoon E Delay E Weiler-Mithoff EM

No local recurrence

No control group

Very short follow up

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 7: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

Implant BR 40g AL

Implant reconstruction

50 g AL

175 m 46 kil

55 g left breast

Breast volume augmentation

Coleman technique

scar

improvement

Immediate Pre-op Intraop after debridement

25 Days Post Op 41 Days Post Op

Intra-op after Cell Tx

14 Days Post Op

90 y old women 40 years after abdominal radiation therapy

and non healing sacral pressure sore Dr Sadanori Akita

90 cells to circular area around sore

10 cells to sore itself

145 days

1994 Osteosarcoma tt

2006 lipofilling

Clinical

results

LR of osteosarcoma

13 y after TT

18 mths after lipofilling

Local recurrence

Kotaro Yoshimura MD

SAFETY OF LIPOFILLING

IN BREAST CANCER PATIENTS

From the lab

to clinical results

FBERTOLINI

IMARTIN PADURA

IEO Milan

NOS DISCLOSURE

Review

ldquoAdipose tissue cells lipotransfer and cancer

A challenge for scientists oncologists and

surgeonsrdquo Francesco Bertolinia

Abdominal or thigh Human WAT

gt150 samples

Immunomagnetic separation

Enzymatic digestion

155 Samples FROM LIPOTRANSFER HAVE BEEN PURIFIED

F BERTOLINIrsquoS LAB

Purified CD34+ WAT-derived cells

COLEMAN TECHNIQUE

Stromal vascular fraction

NSG Females 8 weeks old

cells suspension injected in the fourth mammary fad pad directly though the nipple

Tumors are detectable at day 7 raise 800-1000 mm3 in 35-40 days

106 breast cancer cells 106 breast cancer cells + 2x105 WAT cells

cell suspension in matrigel +blu dye

Transplant of a human breast cell line on the mammary gland of a imunodeficient mouse to develop a breast cancer mouse model

MDA-MB-436 MDA-MB-436 CD34+ WAT cells

0

500

1000

1500

2000

2500

0 29 62 76T

um

or

vo

lum

e (

mm

3)

Days

CD34+

Unfractionated

Control

CD34+ no tumor

Breast cell line 1 (MDA-MB-436)

0

50

100

150

200

250

0 36 63 70 88 95

Tu

mo

r vo

lum

e (

mm

3)

Days

Control

Breast cell line 2 (HCC1937)

Adipose derived CD34+ cells promote breast tumor growth

in vivo

Tumors were bigger when co-transplanted

with adipose cells

hellipand this was true with two different breast cell lines

mastectomy primary tumor

axillary lympho

node metastases

lung

metastases

Injection of CD34+WAT-derived cells increases lung metastases

WAT cells

0

5

10

15

20

25

30

Lung Metastases

Controls

CD34- injected

CD34+ injected

2012

9269 with oncologic FU

Only 29 with a control group (Rigotti - Petit)

Only 1 with a cohort study group (Petit)

Eur J Surg Oncol 2012 May38(5)382-9 Epub 2012 Mar 15

Prospective trial of adipose-derived

regenerative cell (ADRC)-enriched fat grafting

for partial mastectomy defects the RESTORE-

2 trial Peacuterez-Cano R Vranckx JJ Lasso JM Calabrese C Merck B Milstein AM

Sassoon E Delay E Weiler-Mithoff EM

No local recurrence

No control group

Very short follow up

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 8: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

Implant reconstruction

50 g AL

175 m 46 kil

55 g left breast

Breast volume augmentation

Coleman technique

scar

improvement

Immediate Pre-op Intraop after debridement

25 Days Post Op 41 Days Post Op

Intra-op after Cell Tx

14 Days Post Op

90 y old women 40 years after abdominal radiation therapy

and non healing sacral pressure sore Dr Sadanori Akita

90 cells to circular area around sore

10 cells to sore itself

145 days

1994 Osteosarcoma tt

2006 lipofilling

Clinical

results

LR of osteosarcoma

13 y after TT

18 mths after lipofilling

Local recurrence

Kotaro Yoshimura MD

SAFETY OF LIPOFILLING

IN BREAST CANCER PATIENTS

From the lab

to clinical results

FBERTOLINI

IMARTIN PADURA

IEO Milan

NOS DISCLOSURE

Review

ldquoAdipose tissue cells lipotransfer and cancer

A challenge for scientists oncologists and

surgeonsrdquo Francesco Bertolinia

Abdominal or thigh Human WAT

gt150 samples

Immunomagnetic separation

Enzymatic digestion

155 Samples FROM LIPOTRANSFER HAVE BEEN PURIFIED

F BERTOLINIrsquoS LAB

Purified CD34+ WAT-derived cells

COLEMAN TECHNIQUE

Stromal vascular fraction

NSG Females 8 weeks old

cells suspension injected in the fourth mammary fad pad directly though the nipple

Tumors are detectable at day 7 raise 800-1000 mm3 in 35-40 days

106 breast cancer cells 106 breast cancer cells + 2x105 WAT cells

cell suspension in matrigel +blu dye

Transplant of a human breast cell line on the mammary gland of a imunodeficient mouse to develop a breast cancer mouse model

MDA-MB-436 MDA-MB-436 CD34+ WAT cells

0

500

1000

1500

2000

2500

0 29 62 76T

um

or

vo

lum

e (

mm

3)

Days

CD34+

Unfractionated

Control

CD34+ no tumor

Breast cell line 1 (MDA-MB-436)

0

50

100

150

200

250

0 36 63 70 88 95

Tu

mo

r vo

lum

e (

mm

3)

Days

Control

Breast cell line 2 (HCC1937)

Adipose derived CD34+ cells promote breast tumor growth

in vivo

Tumors were bigger when co-transplanted

with adipose cells

hellipand this was true with two different breast cell lines

mastectomy primary tumor

axillary lympho

node metastases

lung

metastases

Injection of CD34+WAT-derived cells increases lung metastases

WAT cells

0

5

10

15

20

25

30

Lung Metastases

Controls

CD34- injected

CD34+ injected

2012

9269 with oncologic FU

Only 29 with a control group (Rigotti - Petit)

Only 1 with a cohort study group (Petit)

Eur J Surg Oncol 2012 May38(5)382-9 Epub 2012 Mar 15

Prospective trial of adipose-derived

regenerative cell (ADRC)-enriched fat grafting

for partial mastectomy defects the RESTORE-

2 trial Peacuterez-Cano R Vranckx JJ Lasso JM Calabrese C Merck B Milstein AM

Sassoon E Delay E Weiler-Mithoff EM

No local recurrence

No control group

Very short follow up

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 9: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

175 m 46 kil

55 g left breast

Breast volume augmentation

Coleman technique

scar

improvement

Immediate Pre-op Intraop after debridement

25 Days Post Op 41 Days Post Op

Intra-op after Cell Tx

14 Days Post Op

90 y old women 40 years after abdominal radiation therapy

and non healing sacral pressure sore Dr Sadanori Akita

90 cells to circular area around sore

10 cells to sore itself

145 days

1994 Osteosarcoma tt

2006 lipofilling

Clinical

results

LR of osteosarcoma

13 y after TT

18 mths after lipofilling

Local recurrence

Kotaro Yoshimura MD

SAFETY OF LIPOFILLING

IN BREAST CANCER PATIENTS

From the lab

to clinical results

FBERTOLINI

IMARTIN PADURA

IEO Milan

NOS DISCLOSURE

Review

ldquoAdipose tissue cells lipotransfer and cancer

A challenge for scientists oncologists and

surgeonsrdquo Francesco Bertolinia

Abdominal or thigh Human WAT

gt150 samples

Immunomagnetic separation

Enzymatic digestion

155 Samples FROM LIPOTRANSFER HAVE BEEN PURIFIED

F BERTOLINIrsquoS LAB

Purified CD34+ WAT-derived cells

COLEMAN TECHNIQUE

Stromal vascular fraction

NSG Females 8 weeks old

cells suspension injected in the fourth mammary fad pad directly though the nipple

Tumors are detectable at day 7 raise 800-1000 mm3 in 35-40 days

106 breast cancer cells 106 breast cancer cells + 2x105 WAT cells

cell suspension in matrigel +blu dye

Transplant of a human breast cell line on the mammary gland of a imunodeficient mouse to develop a breast cancer mouse model

MDA-MB-436 MDA-MB-436 CD34+ WAT cells

0

500

1000

1500

2000

2500

0 29 62 76T

um

or

vo

lum

e (

mm

3)

Days

CD34+

Unfractionated

Control

CD34+ no tumor

Breast cell line 1 (MDA-MB-436)

0

50

100

150

200

250

0 36 63 70 88 95

Tu

mo

r vo

lum

e (

mm

3)

Days

Control

Breast cell line 2 (HCC1937)

Adipose derived CD34+ cells promote breast tumor growth

in vivo

Tumors were bigger when co-transplanted

with adipose cells

hellipand this was true with two different breast cell lines

mastectomy primary tumor

axillary lympho

node metastases

lung

metastases

Injection of CD34+WAT-derived cells increases lung metastases

WAT cells

0

5

10

15

20

25

30

Lung Metastases

Controls

CD34- injected

CD34+ injected

2012

9269 with oncologic FU

Only 29 with a control group (Rigotti - Petit)

Only 1 with a cohort study group (Petit)

Eur J Surg Oncol 2012 May38(5)382-9 Epub 2012 Mar 15

Prospective trial of adipose-derived

regenerative cell (ADRC)-enriched fat grafting

for partial mastectomy defects the RESTORE-

2 trial Peacuterez-Cano R Vranckx JJ Lasso JM Calabrese C Merck B Milstein AM

Sassoon E Delay E Weiler-Mithoff EM

No local recurrence

No control group

Very short follow up

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 10: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

Breast volume augmentation

Coleman technique

scar

improvement

Immediate Pre-op Intraop after debridement

25 Days Post Op 41 Days Post Op

Intra-op after Cell Tx

14 Days Post Op

90 y old women 40 years after abdominal radiation therapy

and non healing sacral pressure sore Dr Sadanori Akita

90 cells to circular area around sore

10 cells to sore itself

145 days

1994 Osteosarcoma tt

2006 lipofilling

Clinical

results

LR of osteosarcoma

13 y after TT

18 mths after lipofilling

Local recurrence

Kotaro Yoshimura MD

SAFETY OF LIPOFILLING

IN BREAST CANCER PATIENTS

From the lab

to clinical results

FBERTOLINI

IMARTIN PADURA

IEO Milan

NOS DISCLOSURE

Review

ldquoAdipose tissue cells lipotransfer and cancer

A challenge for scientists oncologists and

surgeonsrdquo Francesco Bertolinia

Abdominal or thigh Human WAT

gt150 samples

Immunomagnetic separation

Enzymatic digestion

155 Samples FROM LIPOTRANSFER HAVE BEEN PURIFIED

F BERTOLINIrsquoS LAB

Purified CD34+ WAT-derived cells

COLEMAN TECHNIQUE

Stromal vascular fraction

NSG Females 8 weeks old

cells suspension injected in the fourth mammary fad pad directly though the nipple

Tumors are detectable at day 7 raise 800-1000 mm3 in 35-40 days

106 breast cancer cells 106 breast cancer cells + 2x105 WAT cells

cell suspension in matrigel +blu dye

Transplant of a human breast cell line on the mammary gland of a imunodeficient mouse to develop a breast cancer mouse model

MDA-MB-436 MDA-MB-436 CD34+ WAT cells

0

500

1000

1500

2000

2500

0 29 62 76T

um

or

vo

lum

e (

mm

3)

Days

CD34+

Unfractionated

Control

CD34+ no tumor

Breast cell line 1 (MDA-MB-436)

0

50

100

150

200

250

0 36 63 70 88 95

Tu

mo

r vo

lum

e (

mm

3)

Days

Control

Breast cell line 2 (HCC1937)

Adipose derived CD34+ cells promote breast tumor growth

in vivo

Tumors were bigger when co-transplanted

with adipose cells

hellipand this was true with two different breast cell lines

mastectomy primary tumor

axillary lympho

node metastases

lung

metastases

Injection of CD34+WAT-derived cells increases lung metastases

WAT cells

0

5

10

15

20

25

30

Lung Metastases

Controls

CD34- injected

CD34+ injected

2012

9269 with oncologic FU

Only 29 with a control group (Rigotti - Petit)

Only 1 with a cohort study group (Petit)

Eur J Surg Oncol 2012 May38(5)382-9 Epub 2012 Mar 15

Prospective trial of adipose-derived

regenerative cell (ADRC)-enriched fat grafting

for partial mastectomy defects the RESTORE-

2 trial Peacuterez-Cano R Vranckx JJ Lasso JM Calabrese C Merck B Milstein AM

Sassoon E Delay E Weiler-Mithoff EM

No local recurrence

No control group

Very short follow up

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 11: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

Immediate Pre-op Intraop after debridement

25 Days Post Op 41 Days Post Op

Intra-op after Cell Tx

14 Days Post Op

90 y old women 40 years after abdominal radiation therapy

and non healing sacral pressure sore Dr Sadanori Akita

90 cells to circular area around sore

10 cells to sore itself

145 days

1994 Osteosarcoma tt

2006 lipofilling

Clinical

results

LR of osteosarcoma

13 y after TT

18 mths after lipofilling

Local recurrence

Kotaro Yoshimura MD

SAFETY OF LIPOFILLING

IN BREAST CANCER PATIENTS

From the lab

to clinical results

FBERTOLINI

IMARTIN PADURA

IEO Milan

NOS DISCLOSURE

Review

ldquoAdipose tissue cells lipotransfer and cancer

A challenge for scientists oncologists and

surgeonsrdquo Francesco Bertolinia

Abdominal or thigh Human WAT

gt150 samples

Immunomagnetic separation

Enzymatic digestion

155 Samples FROM LIPOTRANSFER HAVE BEEN PURIFIED

F BERTOLINIrsquoS LAB

Purified CD34+ WAT-derived cells

COLEMAN TECHNIQUE

Stromal vascular fraction

NSG Females 8 weeks old

cells suspension injected in the fourth mammary fad pad directly though the nipple

Tumors are detectable at day 7 raise 800-1000 mm3 in 35-40 days

106 breast cancer cells 106 breast cancer cells + 2x105 WAT cells

cell suspension in matrigel +blu dye

Transplant of a human breast cell line on the mammary gland of a imunodeficient mouse to develop a breast cancer mouse model

MDA-MB-436 MDA-MB-436 CD34+ WAT cells

0

500

1000

1500

2000

2500

0 29 62 76T

um

or

vo

lum

e (

mm

3)

Days

CD34+

Unfractionated

Control

CD34+ no tumor

Breast cell line 1 (MDA-MB-436)

0

50

100

150

200

250

0 36 63 70 88 95

Tu

mo

r vo

lum

e (

mm

3)

Days

Control

Breast cell line 2 (HCC1937)

Adipose derived CD34+ cells promote breast tumor growth

in vivo

Tumors were bigger when co-transplanted

with adipose cells

hellipand this was true with two different breast cell lines

mastectomy primary tumor

axillary lympho

node metastases

lung

metastases

Injection of CD34+WAT-derived cells increases lung metastases

WAT cells

0

5

10

15

20

25

30

Lung Metastases

Controls

CD34- injected

CD34+ injected

2012

9269 with oncologic FU

Only 29 with a control group (Rigotti - Petit)

Only 1 with a cohort study group (Petit)

Eur J Surg Oncol 2012 May38(5)382-9 Epub 2012 Mar 15

Prospective trial of adipose-derived

regenerative cell (ADRC)-enriched fat grafting

for partial mastectomy defects the RESTORE-

2 trial Peacuterez-Cano R Vranckx JJ Lasso JM Calabrese C Merck B Milstein AM

Sassoon E Delay E Weiler-Mithoff EM

No local recurrence

No control group

Very short follow up

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 12: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

1994 Osteosarcoma tt

2006 lipofilling

Clinical

results

LR of osteosarcoma

13 y after TT

18 mths after lipofilling

Local recurrence

Kotaro Yoshimura MD

SAFETY OF LIPOFILLING

IN BREAST CANCER PATIENTS

From the lab

to clinical results

FBERTOLINI

IMARTIN PADURA

IEO Milan

NOS DISCLOSURE

Review

ldquoAdipose tissue cells lipotransfer and cancer

A challenge for scientists oncologists and

surgeonsrdquo Francesco Bertolinia

Abdominal or thigh Human WAT

gt150 samples

Immunomagnetic separation

Enzymatic digestion

155 Samples FROM LIPOTRANSFER HAVE BEEN PURIFIED

F BERTOLINIrsquoS LAB

Purified CD34+ WAT-derived cells

COLEMAN TECHNIQUE

Stromal vascular fraction

NSG Females 8 weeks old

cells suspension injected in the fourth mammary fad pad directly though the nipple

Tumors are detectable at day 7 raise 800-1000 mm3 in 35-40 days

106 breast cancer cells 106 breast cancer cells + 2x105 WAT cells

cell suspension in matrigel +blu dye

Transplant of a human breast cell line on the mammary gland of a imunodeficient mouse to develop a breast cancer mouse model

MDA-MB-436 MDA-MB-436 CD34+ WAT cells

0

500

1000

1500

2000

2500

0 29 62 76T

um

or

vo

lum

e (

mm

3)

Days

CD34+

Unfractionated

Control

CD34+ no tumor

Breast cell line 1 (MDA-MB-436)

0

50

100

150

200

250

0 36 63 70 88 95

Tu

mo

r vo

lum

e (

mm

3)

Days

Control

Breast cell line 2 (HCC1937)

Adipose derived CD34+ cells promote breast tumor growth

in vivo

Tumors were bigger when co-transplanted

with adipose cells

hellipand this was true with two different breast cell lines

mastectomy primary tumor

axillary lympho

node metastases

lung

metastases

Injection of CD34+WAT-derived cells increases lung metastases

WAT cells

0

5

10

15

20

25

30

Lung Metastases

Controls

CD34- injected

CD34+ injected

2012

9269 with oncologic FU

Only 29 with a control group (Rigotti - Petit)

Only 1 with a cohort study group (Petit)

Eur J Surg Oncol 2012 May38(5)382-9 Epub 2012 Mar 15

Prospective trial of adipose-derived

regenerative cell (ADRC)-enriched fat grafting

for partial mastectomy defects the RESTORE-

2 trial Peacuterez-Cano R Vranckx JJ Lasso JM Calabrese C Merck B Milstein AM

Sassoon E Delay E Weiler-Mithoff EM

No local recurrence

No control group

Very short follow up

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 13: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

Kotaro Yoshimura MD

SAFETY OF LIPOFILLING

IN BREAST CANCER PATIENTS

From the lab

to clinical results

FBERTOLINI

IMARTIN PADURA

IEO Milan

NOS DISCLOSURE

Review

ldquoAdipose tissue cells lipotransfer and cancer

A challenge for scientists oncologists and

surgeonsrdquo Francesco Bertolinia

Abdominal or thigh Human WAT

gt150 samples

Immunomagnetic separation

Enzymatic digestion

155 Samples FROM LIPOTRANSFER HAVE BEEN PURIFIED

F BERTOLINIrsquoS LAB

Purified CD34+ WAT-derived cells

COLEMAN TECHNIQUE

Stromal vascular fraction

NSG Females 8 weeks old

cells suspension injected in the fourth mammary fad pad directly though the nipple

Tumors are detectable at day 7 raise 800-1000 mm3 in 35-40 days

106 breast cancer cells 106 breast cancer cells + 2x105 WAT cells

cell suspension in matrigel +blu dye

Transplant of a human breast cell line on the mammary gland of a imunodeficient mouse to develop a breast cancer mouse model

MDA-MB-436 MDA-MB-436 CD34+ WAT cells

0

500

1000

1500

2000

2500

0 29 62 76T

um

or

vo

lum

e (

mm

3)

Days

CD34+

Unfractionated

Control

CD34+ no tumor

Breast cell line 1 (MDA-MB-436)

0

50

100

150

200

250

0 36 63 70 88 95

Tu

mo

r vo

lum

e (

mm

3)

Days

Control

Breast cell line 2 (HCC1937)

Adipose derived CD34+ cells promote breast tumor growth

in vivo

Tumors were bigger when co-transplanted

with adipose cells

hellipand this was true with two different breast cell lines

mastectomy primary tumor

axillary lympho

node metastases

lung

metastases

Injection of CD34+WAT-derived cells increases lung metastases

WAT cells

0

5

10

15

20

25

30

Lung Metastases

Controls

CD34- injected

CD34+ injected

2012

9269 with oncologic FU

Only 29 with a control group (Rigotti - Petit)

Only 1 with a cohort study group (Petit)

Eur J Surg Oncol 2012 May38(5)382-9 Epub 2012 Mar 15

Prospective trial of adipose-derived

regenerative cell (ADRC)-enriched fat grafting

for partial mastectomy defects the RESTORE-

2 trial Peacuterez-Cano R Vranckx JJ Lasso JM Calabrese C Merck B Milstein AM

Sassoon E Delay E Weiler-Mithoff EM

No local recurrence

No control group

Very short follow up

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 14: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

SAFETY OF LIPOFILLING

IN BREAST CANCER PATIENTS

From the lab

to clinical results

FBERTOLINI

IMARTIN PADURA

IEO Milan

NOS DISCLOSURE

Review

ldquoAdipose tissue cells lipotransfer and cancer

A challenge for scientists oncologists and

surgeonsrdquo Francesco Bertolinia

Abdominal or thigh Human WAT

gt150 samples

Immunomagnetic separation

Enzymatic digestion

155 Samples FROM LIPOTRANSFER HAVE BEEN PURIFIED

F BERTOLINIrsquoS LAB

Purified CD34+ WAT-derived cells

COLEMAN TECHNIQUE

Stromal vascular fraction

NSG Females 8 weeks old

cells suspension injected in the fourth mammary fad pad directly though the nipple

Tumors are detectable at day 7 raise 800-1000 mm3 in 35-40 days

106 breast cancer cells 106 breast cancer cells + 2x105 WAT cells

cell suspension in matrigel +blu dye

Transplant of a human breast cell line on the mammary gland of a imunodeficient mouse to develop a breast cancer mouse model

MDA-MB-436 MDA-MB-436 CD34+ WAT cells

0

500

1000

1500

2000

2500

0 29 62 76T

um

or

vo

lum

e (

mm

3)

Days

CD34+

Unfractionated

Control

CD34+ no tumor

Breast cell line 1 (MDA-MB-436)

0

50

100

150

200

250

0 36 63 70 88 95

Tu

mo

r vo

lum

e (

mm

3)

Days

Control

Breast cell line 2 (HCC1937)

Adipose derived CD34+ cells promote breast tumor growth

in vivo

Tumors were bigger when co-transplanted

with adipose cells

hellipand this was true with two different breast cell lines

mastectomy primary tumor

axillary lympho

node metastases

lung

metastases

Injection of CD34+WAT-derived cells increases lung metastases

WAT cells

0

5

10

15

20

25

30

Lung Metastases

Controls

CD34- injected

CD34+ injected

2012

9269 with oncologic FU

Only 29 with a control group (Rigotti - Petit)

Only 1 with a cohort study group (Petit)

Eur J Surg Oncol 2012 May38(5)382-9 Epub 2012 Mar 15

Prospective trial of adipose-derived

regenerative cell (ADRC)-enriched fat grafting

for partial mastectomy defects the RESTORE-

2 trial Peacuterez-Cano R Vranckx JJ Lasso JM Calabrese C Merck B Milstein AM

Sassoon E Delay E Weiler-Mithoff EM

No local recurrence

No control group

Very short follow up

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 15: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

Abdominal or thigh Human WAT

gt150 samples

Immunomagnetic separation

Enzymatic digestion

155 Samples FROM LIPOTRANSFER HAVE BEEN PURIFIED

F BERTOLINIrsquoS LAB

Purified CD34+ WAT-derived cells

COLEMAN TECHNIQUE

Stromal vascular fraction

NSG Females 8 weeks old

cells suspension injected in the fourth mammary fad pad directly though the nipple

Tumors are detectable at day 7 raise 800-1000 mm3 in 35-40 days

106 breast cancer cells 106 breast cancer cells + 2x105 WAT cells

cell suspension in matrigel +blu dye

Transplant of a human breast cell line on the mammary gland of a imunodeficient mouse to develop a breast cancer mouse model

MDA-MB-436 MDA-MB-436 CD34+ WAT cells

0

500

1000

1500

2000

2500

0 29 62 76T

um

or

vo

lum

e (

mm

3)

Days

CD34+

Unfractionated

Control

CD34+ no tumor

Breast cell line 1 (MDA-MB-436)

0

50

100

150

200

250

0 36 63 70 88 95

Tu

mo

r vo

lum

e (

mm

3)

Days

Control

Breast cell line 2 (HCC1937)

Adipose derived CD34+ cells promote breast tumor growth

in vivo

Tumors were bigger when co-transplanted

with adipose cells

hellipand this was true with two different breast cell lines

mastectomy primary tumor

axillary lympho

node metastases

lung

metastases

Injection of CD34+WAT-derived cells increases lung metastases

WAT cells

0

5

10

15

20

25

30

Lung Metastases

Controls

CD34- injected

CD34+ injected

2012

9269 with oncologic FU

Only 29 with a control group (Rigotti - Petit)

Only 1 with a cohort study group (Petit)

Eur J Surg Oncol 2012 May38(5)382-9 Epub 2012 Mar 15

Prospective trial of adipose-derived

regenerative cell (ADRC)-enriched fat grafting

for partial mastectomy defects the RESTORE-

2 trial Peacuterez-Cano R Vranckx JJ Lasso JM Calabrese C Merck B Milstein AM

Sassoon E Delay E Weiler-Mithoff EM

No local recurrence

No control group

Very short follow up

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 16: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

NSG Females 8 weeks old

cells suspension injected in the fourth mammary fad pad directly though the nipple

Tumors are detectable at day 7 raise 800-1000 mm3 in 35-40 days

106 breast cancer cells 106 breast cancer cells + 2x105 WAT cells

cell suspension in matrigel +blu dye

Transplant of a human breast cell line on the mammary gland of a imunodeficient mouse to develop a breast cancer mouse model

MDA-MB-436 MDA-MB-436 CD34+ WAT cells

0

500

1000

1500

2000

2500

0 29 62 76T

um

or

vo

lum

e (

mm

3)

Days

CD34+

Unfractionated

Control

CD34+ no tumor

Breast cell line 1 (MDA-MB-436)

0

50

100

150

200

250

0 36 63 70 88 95

Tu

mo

r vo

lum

e (

mm

3)

Days

Control

Breast cell line 2 (HCC1937)

Adipose derived CD34+ cells promote breast tumor growth

in vivo

Tumors were bigger when co-transplanted

with adipose cells

hellipand this was true with two different breast cell lines

mastectomy primary tumor

axillary lympho

node metastases

lung

metastases

Injection of CD34+WAT-derived cells increases lung metastases

WAT cells

0

5

10

15

20

25

30

Lung Metastases

Controls

CD34- injected

CD34+ injected

2012

9269 with oncologic FU

Only 29 with a control group (Rigotti - Petit)

Only 1 with a cohort study group (Petit)

Eur J Surg Oncol 2012 May38(5)382-9 Epub 2012 Mar 15

Prospective trial of adipose-derived

regenerative cell (ADRC)-enriched fat grafting

for partial mastectomy defects the RESTORE-

2 trial Peacuterez-Cano R Vranckx JJ Lasso JM Calabrese C Merck B Milstein AM

Sassoon E Delay E Weiler-Mithoff EM

No local recurrence

No control group

Very short follow up

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 17: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

MDA-MB-436 MDA-MB-436 CD34+ WAT cells

0

500

1000

1500

2000

2500

0 29 62 76T

um

or

vo

lum

e (

mm

3)

Days

CD34+

Unfractionated

Control

CD34+ no tumor

Breast cell line 1 (MDA-MB-436)

0

50

100

150

200

250

0 36 63 70 88 95

Tu

mo

r vo

lum

e (

mm

3)

Days

Control

Breast cell line 2 (HCC1937)

Adipose derived CD34+ cells promote breast tumor growth

in vivo

Tumors were bigger when co-transplanted

with adipose cells

hellipand this was true with two different breast cell lines

mastectomy primary tumor

axillary lympho

node metastases

lung

metastases

Injection of CD34+WAT-derived cells increases lung metastases

WAT cells

0

5

10

15

20

25

30

Lung Metastases

Controls

CD34- injected

CD34+ injected

2012

9269 with oncologic FU

Only 29 with a control group (Rigotti - Petit)

Only 1 with a cohort study group (Petit)

Eur J Surg Oncol 2012 May38(5)382-9 Epub 2012 Mar 15

Prospective trial of adipose-derived

regenerative cell (ADRC)-enriched fat grafting

for partial mastectomy defects the RESTORE-

2 trial Peacuterez-Cano R Vranckx JJ Lasso JM Calabrese C Merck B Milstein AM

Sassoon E Delay E Weiler-Mithoff EM

No local recurrence

No control group

Very short follow up

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 18: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

mastectomy primary tumor

axillary lympho

node metastases

lung

metastases

Injection of CD34+WAT-derived cells increases lung metastases

WAT cells

0

5

10

15

20

25

30

Lung Metastases

Controls

CD34- injected

CD34+ injected

2012

9269 with oncologic FU

Only 29 with a control group (Rigotti - Petit)

Only 1 with a cohort study group (Petit)

Eur J Surg Oncol 2012 May38(5)382-9 Epub 2012 Mar 15

Prospective trial of adipose-derived

regenerative cell (ADRC)-enriched fat grafting

for partial mastectomy defects the RESTORE-

2 trial Peacuterez-Cano R Vranckx JJ Lasso JM Calabrese C Merck B Milstein AM

Sassoon E Delay E Weiler-Mithoff EM

No local recurrence

No control group

Very short follow up

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 19: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

2012

9269 with oncologic FU

Only 29 with a control group (Rigotti - Petit)

Only 1 with a cohort study group (Petit)

Eur J Surg Oncol 2012 May38(5)382-9 Epub 2012 Mar 15

Prospective trial of adipose-derived

regenerative cell (ADRC)-enriched fat grafting

for partial mastectomy defects the RESTORE-

2 trial Peacuterez-Cano R Vranckx JJ Lasso JM Calabrese C Merck B Milstein AM

Sassoon E Delay E Weiler-Mithoff EM

No local recurrence

No control group

Very short follow up

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 20: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

Eur J Surg Oncol 2012 May38(5)382-9 Epub 2012 Mar 15

Prospective trial of adipose-derived

regenerative cell (ADRC)-enriched fat grafting

for partial mastectomy defects the RESTORE-

2 trial Peacuterez-Cano R Vranckx JJ Lasso JM Calabrese C Merck B Milstein AM

Sassoon E Delay E Weiler-Mithoff EM

No local recurrence

No control group

Very short follow up

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 21: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

bull 321 breast cancer patients

who subsequently underwent

lipofilling Coleman technique

bull 642 matched-patients with

similar characteristics who did

not undergo a lipofilling

Annals of Oncology 2011 may 24

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 22: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

Matching criteriae

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 23: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

+6 months

Washing out

period

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 24: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

BCT

mastectomy

C Invasif

DCIS

plt 0001

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 25: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

CONCLUSION

Matched Cohort Control Study I

1 No evidence of increasing risk of

LRR after Lipofilling on the whole

population

2- Significant increase of local

recurrence rate in the group of

intra epithelial neoplasia (DCIS

LCIS)

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 26: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

bull 59 IN SITU breast cancer

patients who subsequently

underwent lipofilling

(Coleman technique)

bull 118 IN SITU matched-patients

with similar characteristics who

did not undergo a lipofilling Annals of Oncology (in press)

EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA

EPITHELIAL NEOPLASIA A MATCHED COHORT STUDY

Jean Yves Petit1 Mario Rietjens1 Edoardo

Botteri2 Nicole Rotmensz2 Francesco Bertolini3

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 27: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

Lipofilling

n ()

Controls

n () p

All patients 59 118

Age at first

surgery (years) Median (range) 46 (30-64) 47 (26-69)

Matching

Variable

Age at

baseline (years) Median (range) 49 (33-65) 50 (29-72)

Matching

Variable

Time to baseline

from surgery

le 1 year

1 -2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

38 (322)

26 (220)

20 (170)

34 (288)

Matching

Variable

Histology DIN

LIN

57 (966)

2 (34)

114 (966)

4 (34)

Matching

Variable

Year of surgery

lsquo00-lsquo03

lsquo04-lsquo06

lsquo07-lsquo10

7 (119)

30 (509)

22 (373)

18 (153)

65 (551)

35 (297)

Matching

Variable

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

Matching

Variable

Estrogen receptora Positive

Negative

44 (800)

11 (200)

88 (800)

22 (200)

Matching

Variable

Progesteron

receptora

Positive

Negative

41 (746)

14 (256)

83 (728)

31 (272) 081

Gradea

1

2

3

11 (196)

28 (500)

17 (304)

17 (145)

75 (641)

25 (214)

021

Ki-67 a lt 14

ge 14

25 (439)

32 (561)

55 (483)

59 (518) 059

Her2neua Not Overexpressed

Overexpressed

34 (642)

19 (359)

74 (673)

36 (327) 069

Margin statusa

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

18 (783)

4 (174)

1 (44)

038

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

55 (625)

33 (375) 090

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

6 (250)

8 (333)

10 (417)

091

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 28: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

Local recurrences characteristics

Lipo-

filling

Age at

baseline

Surgery

for the

primary

Location

of the

primary

Histology of the

primary

Grad

e

Margin

Surgery

for the

relapse

Location

of the

relapse

Histology of the

relapse

Grad

e

Lipofilling

(CC)

Lipofilling

location

Time from

primary

surgery to local

relapse

Time from

lipofilling to

local relapse

Yes 46 QUAD QSI DIN

Comedo +

Micropapillar

y

3 N NSM QSI DIN

Solid +

necrosis +

comedo

3 64 QSI QII 28 24

Yes 45 QUAD QSE DIN Cribriform +

Necrosis 3 N NSM QSE

DIN +

IDC

Solid +

necrosis 3 40 QSE 21 7

Yes 62 SSM QSE DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE QSE IDC NR NR 35 QSIQSE 62 12

Yes 41 SSM QSI DIN

Cribriforme +

Micropapillar

y + Papillary +

Necrosis

2 N WE QE DIN NR NR 90 QSIQSE 48 5

Yes 39 TM QSE DIN

Cribiforme +

micropapillar

y + Necrosis

2 N WE QSE IDC papillary 1 27 QSI 30 14

Yes 45 NSM QSI QII DIN Cribiforme +

Solid 3 N WE QSE

DIN +

IDC

Solid +

necrosis 3 37 QIIQIE 26 11

No 39 NSM QI DIN Cribriform +

Necrosis 2 N WE

Retro

areolar DIN

Micropapillar

y 2 na na 48 na

No 45 NSM QSI DIN

Cribriform +

Micropapillar

y + Necrosis

2 N WE Retro

areolar DIN

Cribriform +

Micropapillar

y + Necrosis

2 na na 65 na

No 47 SSM QII DIN Papillary 2 N WE QE DIN +

IDC Cribriform 1 na na 56 na

Quadrantectomy

Mastectomy

12 (203)

47 (797)

24 (203)

94 (797)

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 29: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

At risk

()

Events

(5-year cum inc ) p

All patients 59 6 (178)

Age at lipofilling lt 50 years

ge 50 years

30 (508)

29 (492)

5 (231)

1 (47) 007

Histology DIN

LIN

57 (966)

2 (34)

6 (190)

0 (00) 055

Time to baseline

from surgery

le 1 year

11-2 years

21-3 years

gt 3 years

19 (322)

13 (220)

10 (170)

17 (288)

4 (377)

1 (77)

1 (100)

0 (00)

009

Type of surgery Quadrantectomy

Mastectomy

12 (203)

47 (797)

2 (167)

4 (184) 040

Estrogen receptor Positive

Negative

44 (800)

11 (200)

5 (203)

1 (91) 099

Progesteron

receptor

Positive

Negative

41 (746)

14 (256)

4 (140)

2 (536) 054

Grade

1

2

3

11 (196)

28 (500)

17 (304)

0 (00)

3 (214)

3 (NA)

006

Ki-67 lt 14

ge 14

25 (439)

32 (561)

1 (40)

5 (329)

013

003a

Her2neu Not Overexpressed

Overexpressed

34 (642)

19 (359)

4 (200)

2 (105) 075

Margin status

after quadrantectomy

Negative (ge 1mm)

Close (lt 1mm)

Positive

7 (583)

3 (250)

2 (167)

1 (143)

1 (333)

0 (00)

084

Hormone therapy

Estrogen receptor positive

Any

None

28 (636)

16 (364)

3 (164)

2 (300) 083

Radiotherapy

after quadrantectomy

Standard

ELIOT

No

4 (333)

3 (250)

5 (417)

1 (250)

1 (333)

0 (00)

046

RISK FACTORS

OF LOCO

REGIONAL

EVENT

IN THE

LIPOFILLING

GROUP

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 30: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

Years from baseline

Cu

mu

lativ

e In

cid

en

ce

00

01

02

03

04

05

0 1 2 3 4 5

P-value 002

HRLipo vs No lipo=45 (95 CI 11-182)

5-year cumulative incidence

Lipofilling 18

No Lipofilling 3

No Lipofilling

Lipofilling

At risk

Lipofilling 59 57 40 30 18 4

No Lipofilling 118 117 107 78 44 16

LR

18

3

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 31: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

Years from baselineC

um

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=30

No Lipofilling n=53

Age at lipofilling lt 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=29

No Lipofilling n=65

Age at lipofilling gt= 50 years

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=39

No Lipofilling n=92

G1 and G2

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=17

No Lipofilling n=25

G3

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=25

No Lipofilling n=55

Ki-67 lt 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=32

No Lipofilling n=59

Ki-67 gt= 14

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=12

No Lipofilling n=24

Quadrantectomy

Years from baseline

Cum

ula

tive Incid

ence

00

01

02

03

04

05

0 1 2 3 4 5

Lipofilling n=47

No Lipofilling n=94

Mastectomy

P-value 002

P-value 058

P-value 023

P-value 003

P-value 089

P-value lt001

P-value 004

P-value 011

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 32: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

CONCLUSION

INCREASING RISK OF LOCAL

RECURRENCES AFTER LIPOFILLING

IN PATIENTS TREATED FOR NON

INVASIVE BREAST CANCER

Strength matched cohort study

But conclusion should be considered

cautiously

small series

short follow up

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells

Page 33: LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic … · MDA-MB-436 MDA-MB-436 CD34+ WAT cells 0 500 1000 1500 2000 2500 0 29 62 76) Days CD34+ Unfractionated Control CD34+,

CONCLUSION

FURTHER STUDIES ARE REQUIRED

ESPECIALLY WITH LIPOFILLING

USING STEM CELLS ENHANCEMENT

assuming the increasing risk of

cancer stimulation with an increasing

concentration of stem cells