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