Breast CancerBreast Cancer

The most frequently diagnosed cancer in women globally.The most frequently diagnosed cancer in women globally.

Second leading cause of cancer deaths in women.Second leading cause of cancer deaths in women.

Accounts for approximately 15% of female cancer deaths.Accounts for approximately 15% of female cancer deaths.

One in eight American women is destined to develop breast One in eight American women is destined to develop breast cancer during her lifetime.cancer during her lifetime.

Risk of recurrence and deathRisk of recurrence and death

from breast cancerfrom breast cancer

Adjuvant systemic Adjuvant systemic therapytherapy

Associated risksAssociated risks

Prognostic factor -Prognostic factor - any measurement available at the time of surgery or diagnosis that correlates with disease-free or overall survival in the absence of systemic adjuvant therapy, useful to be able to optimally select patients who are most likely to benefit from adjuvant systemic therapy.

Predictive factor - Predictive factor - any assessment associated with response to a given therapy, useful to be able to select the optimal adjuvant therapy for an individual patient.

Most common prognostic and predictive Most common prognostic and predictive factors for breast cancerfactors for breast cancer

Steroid receptor status (ER and PR)Steroid receptor status (ER and PR)

HER-2/neu statusHER-2/neu status

Steroid receptor status (ER and PR)Steroid receptor status (ER and PR)

HER-2/neu statusHER-2/neu status

HER-2/neuHER-2/neu

Both prognostic and predictive.

Prognostic factor associated with tumor aggressiveness, increased rate of recurrence and increased mortality.

Optimal use as a predictive factor especially in predicting response to trastuzumab in matastatic setting.

Predictive role for response to chemotherapy and endocrine therapy.

Inversely related with ER expression.

Hormonal ReceptorsHormonal Receptors

Both prognostic and predictive.

Powerful predictive factor for

likelihood of benefit from

adjuvant tamoxifen.

Optimal use as a predictive

factor.

Limited prognostic

significance.

Aim of StudyAim of Study

To identify the significance of HER-2 and hormonal receptor status in patients with locally advanced breast cancer treated with neoadjuvant systemic therapy.

Objectives of StudyObjectives of Study

1. To determine the significance of HER-2 and hormonal receptor status in prognosis of breast cancer patients treated with neoadjuvant systemic therapy.

2. To determine the significance of HER-2 and hormonal receptor status in predicting clinical response to neoadjuvant systemic therapy.

Treatment Plan and Patient Evaluation

• Primary systemic treatment:

- 18 patients (56.2%) with CAF

- 2 patients (6.2) with CMF

- 1 patient (3.1%) with Taxane-based regimen (AT)

- 12 patients (34.2%) with other taxane-based regimen including Herceptin

[3 (21.9%) with TCH, 4 (6.2%) with TNH, 5 (6.2%) with AC)]

Patients and MethodsPatients and Methods

Retrospective study.

Patients

• 32 patients with locally advanced breast cancer (Blokhin Cancer Research Center, Russia, 2005-2009) who received primary systemic treatment.

• AJCC stages IIB, IIIA, IIIB, IIIC and IV (with ipsilateral supraclavicular lymph node involvement only).

Treatment Plan and Patient Evaluation (Continued)

• Standard surgical procedure : modified radical mastectomy.

• Adjuvant radiotherapy in 24 patients (75%).

• HR-positive patients received adjuvant endocrine therapy.

• Follow-up: every 3 months for the first 2 years, every 6 months in the next 3 years, and annually thereafter.

Patients and MethodsPatients and Methods

Classification of Groups• HER-2 receptor positive (HER-2 positive).• HER-2 receptor negative (HER-2 negative).• Hormonal receptor positive (ER and/or PR positive).• Hormonal receptor negative (ER and PR negative).• ER and PR status: determined on the basis of IHC staining.• HER-2 positivity: IHC 3+, or HER-2 amplification on the basis of

FISH (ratio > 2.0) if IHC 2+.Statistical Analysis• MedCalc software version 9.6.2.0.• Frequency table and x2 test to compare the distribution of baseline

characteristics.• Log-rank test for comparisons between subgroups.• Kaplan-Meier method for survival analysis.• Clinical response to neoadjuvant systemic therapy: RECIST

criteria.

ResultsResults

Characteristics Number(n=32) Percentage

Age at diagnosis (Years)

<35

35-50

>50

2

15

15

6.2

46.9

46.9

Menstrual status

Premenopausal

Postmenopausal

15

17

46.9

53.1

Morphological stage

IIB

IIIA

IIIB

IIIC

IV

7

12

7

4

2

21.9

37.5

21.9

12.5

6.2

Tumor size

T1

T2

T3

T4

1

13

9

9

3.1

40.6

28.1

28.1

Nodal status

N0

N1

N2

N3

4

13

11

4

12.5

40.6

34.4

12.5

Distribution of Patient Baseline Distribution of Patient Baseline Characteristics (n=32)Characteristics (n=32)

Distribution of Patient Baseline Distribution of Patient Baseline Characteristics (n=32)Characteristics (n=32)Characteristics Number(n=32) Percentage

Histological grade

1

2

3

Not known

0

15

9

8

0

46.9

28.1

25.0

Histological type

Ductal

Lobular

Mixed

Others

24

4

2

2

75.0

12.5

6.2

6.2

LVI

Yes

No

Not known

3

21

8

9.4

65.6

25.0

HER-2 receptor

Overexpressed/amplified

No

16

16

50.0

50.0

Hormone receptor

Both ER and PR positive

ER/PR positive

ER and PR negative

13

19

13

40.6

59.4

40.6

Distribution of Patient Baseline Distribution of Patient Baseline Characteristics (n=32)Characteristics (n=32)Characteristics Number(n=32) Percentage

Neoadjuvant regimens

CAF

CMF

Taxane-based and others

18

2

12

56.2

6.2

37.5

Surgery

Modified radical mastectomy

Radical mastectomy

Not done

26

3

3

81.2

9.4

9.4

Adjuvant radiation therapy

Yes

No

24

8

75.0

25.0

Adjuvant endocrine therapy

Yes

No

19

13

59.4

40.6

Patient Patient Baseline Characteristics Stratified byBaseline Characteristics Stratified byHormonal Receptor Status and HER-2 Hormonal Receptor Status and HER-2

OverexpressionOverexpression

Characterstics

All

patients

n=32

HER-2 overexpression

P

Hormone receptor

PPositive

n(%)

n=16

Negative

n(%)

n=16

Positive

n(%)

n=19

Negative

n(%)

n=13

Age

<35

35-50

>50

2

15

15

1(6.3)

7(43.8)

8(50.0)

1(6.3)

8(50.0)

7(43.8)

0.941(5.3)

6(31.6)

12(61.2)

1(7.8)

9(69.2)

3(23.1)

0.08

Menstrual status

Premenopausal

Postmenopausal

15

17

8(50.0)

8(50.0)

7(43.8)

9(56.3)

1.00 11(57.9)

8(42.1)

4(30.8)

9(69.2)

0.25

Morphological stage

IIB

IIIA

IIIB

IIIC

IV

7

12

7

4

2

3(18.8)

4(25.0)

4(25.0)

3(18.8)

2(12.5)

4(25.0)

8(50.0)

3(18.8)

1(6.3)

0(0)

0.33

5(26.3)

9(47.4)

3(15.8)

2(10.5)

0(0)

2(15.4)

3(23.1)

4(30.8)

2(15.4)

2(15.4)

0.24

Histological grade

1

2

3

Not known

0

15

9

8

0(0)

2(12.5)

9(56.3)

5(31.3)

0(0)

6(37.5)

6(37.5)

4(25.0)

0.26

0(0)

8(42.1)

9(47.4)

2(10.5)

0(0)

0(0)

6(46.1)

7(53.9)

0.005*

Correlation between Patient Characteristics and Correlation between Patient Characteristics and Clinical ResponseClinical Response

Characteristics All patients (n=32)Clinical response

n(%)P value

Age at diagnosis (Years)

<35

35-50

>50

2

15

15

1(50.0)

6(40.0)

8(53.3)

0.76

Menstrual status

Premenopausal

Postmenopausal

15

17

7(46.7)

8(47.1)

0.74

Morphological stage

IIB

IIIA

IIIB

IIIC

IV

7

12

7

4

2

1(14.3)

6(50.0)

5(71.4)

2(50.0)

1(50.0)

0.31

Tumor size

T1

T2

T3

T4

1

13

9

9

0(0)

7(53.8)

3(33.3)

5(55.6)

0.56

Nodal status

N0

N1

N2

N3

4

13

11

4

2(50.0)

7(53.8)

4(36.4)

2(50.0)

0.86

Correlation between Patient Characteristics and Correlation between Patient Characteristics and Clinical ResponseClinical Response

Characteristics All patients (n=32)Clinical response

n(%)P value

Histological grade

1

2

3

Not known

0

15

9

8

0(0)

1(6.7)

9(100)

5(62.5)

0.08

HER-2 receptor

Overexpressed/amplified

No

16

16

7(43.5)

8(50)

1.0

Hormone receptor

Positive

Negative

19

13

7(36.8)

8(61.5)

0.31

Neoadjuvant regimens

CAF

CMF

Taxane-based and others

18

2

12

8(44.4)

0(0)

7(58.3)

0.29

Mean OS

HER-2 + 36.25 months

HER-2 - 41.5 months

Logrank test P = 0.03

(a)(a) By HER-2 Receptor StatusBy HER-2 Receptor Status

Kaplan-Meier Analysis of Overall SurvivalKaplan-Meier Analysis of Overall Survival

Mean OS

HR + 41 months

HR - 36.5 months

Logrank test P = 0.0009

(b) By Hormonal Receptor Status(b) By Hormonal Receptor Status

Kaplan-Meier Analysis of Overall SurvivalKaplan-Meier Analysis of Overall Survival

Kaplan-Meier Analysis of Progression Free Kaplan-Meier Analysis of Progression Free Survival Survival

Mean PFS

HER-2 + 14 months

HER-2 - 22 months

Logrank test P = 0.14

(a) By HER-2 Receptor Status(a) By HER-2 Receptor Status

(b) By Hormonal Receptor Status(b) By Hormonal Receptor Status

Kaplan-Meier Analysis of Progression Free Kaplan-Meier Analysis of Progression Free Survival Survival

Univariate Univariate Analysis of Prognostic FactorsAnalysis of Prognostic Factors

Factors

OS

P

PFS

P

HR 95% CI HR 95% CI

Age

< 50

≤ 50

0.76

Reference

0.36-1.54

Reference

0.43 0.94

Reference

0.44-1.95

Reference

0.84

Tumor size

T1-2

T3-4

1.07

Reference

0.51-2.25

Reference0.85

0.84

Reference

0.38-1.72

Reference

0.59

Node

N0-1

N2-3

0.83

Reference

0.39-1.68

Reference

0.58 0.63

Reference

0.25-1.23

Reference

0.15

Morphological staging

IIB/IIIA-IIIB

IIIC & IV

0.65

Reference

0.19-1.70

Reference

0.32 Reference

5.62

Reference

15.31-751.77

< 0.0001*

HER-2

Positive

Negative

1.96

Reference

1.07-5.33

Reference

0.03* 1.59

Reference

0.82-3.93

Reference

0.14

Hormone receptor

Positive

Negative

Reference

2.87

Reference

1.92-12.76

0.0009* Reference

2.52

Reference

1.66-11.13

0.003*

Several limitations were encountered in this study due to the relatively small numbers of the subgroups and retrospective design of the study. Some data like histological grading and lymphovascular invasion (LVI) of the tumor could not be traced enough.

Significant association (P = 0.005) between hormonal receptor negativity and high tumor grade.

Highly significant prognostic effect of morphological staging on PFS (P < 0.0001, HR for stage IIIC and IV = 5.62 in comparing with stage IIB, IIIA and IIIB, 95% CI = 15.31-751.77).

This study failed to reveal any statistically significant correlation between clinical response and clinicopathological factors.

DiscussionDiscussion

Significant prognostic effect of HER-2 receptor status on OS (P = 0.03, HR = 1.96, 95% CI = 1.07-5.33).

Significant prognostic effect of hormonal receptor status on OS (P = 0.0009, HR = 2.87, 95% CI = 1.92-12.76).

Significant prognostic effect of hormonal receptor status on PFS (P = 0.0027, HR = 2.52, 95% CI = 1.66-11.13).

DiscussionDiscussion

ConclusionsConclusions

According to this study, it is concluded that hormonal receptor status has significant prognostic effect on both OS and PFS while HER-2 receptor status has significant prognostic effect only on OS despite of having poor prognosis in regarding with PFS. It may probably be due to the fact that this study was only a retrospective study on a very small population. It was also observed that hormonal receptor negative patients had more advanced histological grades.

However, no significant association with clinical response to neoadjuvant chemotherapy was found.

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