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.
Breast Cancer Breast Cancer AwarenessAwareness