Breast Cancer <ul><li>The most frequently diagnosed cancer in women globally. </li></ul><ul><li>Second leading cause of ca...
<ul><li>Risk of recurrence and death </li></ul><ul><li>from breast cancer </li></ul>Adjuvant systemic therapy Associated r...
<ul><li>Prognostic factor -   any measurement available at the time of surgery or diagnosis that correlates with disease-f...
Most common prognostic and predictive factors for breast cancer <ul><li>Steroid receptor status (ER and PR) </li></ul><ul>...
HER-2/neu <ul><li>Both prognostic and predictive. </li></ul><ul><li>Prognostic factor associated with tumor aggressiveness...
Hormonal Receptors <ul><li>Both prognostic and predictive. </li></ul><ul><li>Powerful predictive factor for  likelihood of...
Aim of Study <ul><li>To identify the significance of HER-2 and hormonal receptor status in patients with locally advanced ...
Patients and Methods <ul><li>Retrospective study. </li></ul><ul><li>Patients </li></ul><ul><ul><li>32 patients with locall...
<ul><li>Treatment Plan and Patient Evaluation (Continued) </li></ul><ul><ul><li>Standard surgical procedure : modified rad...
Patients and Methods <ul><li>Classification of Groups </li></ul><ul><ul><li>HER-2 receptor positive (HER-2 positive). </li...
Results
Distribution of Patient Baseline Characteristics (n=32) Characteristics Number(n=32) Percentage Age at diagnosis  (Years) ...
Distribution of Patient Baseline Characteristics (n=32) Characteristics Number(n=32) Percentage Histological grade 1 2 3 N...
Distribution of Patient Baseline Characteristics (n=32) Characteristics Number(n=32) Percentage Neoadjuvant regimens CAF C...
Patient  Baseline Characteristics Stratified by Hormonal Receptor Status and HER-2 Overexpression Characterstics All patie...
Correlation between Patient Characteristics and Clinical Response Characteristics All patients (n=32) Clinical response n(...
Correlation between Patient Characteristics and Clinical Response Characteristics All patients (n=32) Clinical response n(...
Kaplan-Meier Analysis of Overall Survival Mean OS HER-2 +    36.25 months HER-2 -    41.5 months Logrank test  P = 0.03 <u...
Kaplan-Meier Analysis of Overall Survival Mean OS HR +    41 months HR -    36.5 months Logrank test  P = 0.0009 (b) By Ho...
Kaplan-Meier Analysis of Progression Free Survival  Mean PFS HER-2 +    14 months HER-2 -    22 months Logrank test  P = 0...
Kaplan-Meier Analysis of Progression Free Survival  (b) By Hormonal Receptor Status
Univariate  Analysis of Prognostic Factors Factors OS P PFS P HR 95% CI HR 95% CI Age < 50 ≤   50 0.76 Reference 0.36-1.54...
<ul><li>Several limitations were encountered in  this study due to the relatively small numbers of the subgroups and retro...
Discussion <ul><li>Significant prognostic effect of HER-2 receptor status on OS  (P = 0.03, HR = 1.96, 95% CI = 1.07-5.33)...
Conclusions <ul><li>According to this study, it is concluded that hormonal receptor status has significant prognostic effe...
Breast Cancer Awareness
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Pyae phyo aung's thesis (breast cancer)

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Pyae phyo aung's thesis (breast cancer)

  1. 2. Breast Cancer <ul><li>The most frequently diagnosed cancer in women globally. </li></ul><ul><li>Second leading cause of cancer deaths in women. </li></ul><ul><li>Accounts for approximately 15% of female cancer deaths. </li></ul><ul><li>One in eight American women is destined to develop breast cancer during her lifetime. </li></ul>
  2. 3. <ul><li>Risk of recurrence and death </li></ul><ul><li>from breast cancer </li></ul>Adjuvant systemic therapy Associated risks
  3. 4. <ul><li>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. </li></ul><ul><li>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. </li></ul>
  4. 5. Most common prognostic and predictive factors for breast cancer <ul><li>Steroid receptor status (ER and PR) </li></ul><ul><li>HER-2/neu status </li></ul>
  5. 6. HER-2/neu <ul><li>Both prognostic and predictive. </li></ul><ul><li>Prognostic factor associated with tumor aggressiveness, increased rate of recurrence and increased mortality. </li></ul><ul><li>Optimal use as a predictive factor especially in predicting response to trastuzumab in matastatic setting. </li></ul><ul><li>Predictive role for response to chemotherapy and endocrine therapy. </li></ul><ul><li>Inversely related with ER expression. </li></ul>
  6. 7. Hormonal Receptors <ul><li>Both prognostic and predictive. </li></ul><ul><li>Powerful predictive factor for likelihood of benefit from adjuvant tamoxifen. </li></ul><ul><li>Optimal use as a predictive factor. </li></ul><ul><li>Limited prognostic significance. </li></ul>
  7. 8. Aim of Study <ul><li>To identify the significance of HER-2 and hormonal receptor status in patients with locally advanced breast cancer treated with neoadjuvant systemic therapy. </li></ul><ul><li>Objectives of Study </li></ul><ul><li>To determine the significance of HER-2 and hormonal receptor status in prognosis of breast cancer patients treated with neoadjuvant systemic therapy. </li></ul><ul><li>To determine the significance of HER-2 and hormonal receptor status in predicting clinical response to neoadjuvant systemic therapy. </li></ul>
  8. 9. Patients and Methods <ul><li>Retrospective study. </li></ul><ul><li>Patients </li></ul><ul><ul><li>32 patients with locally advanced breast cancer ( Blokhin Cancer Research Center, Russia, 2005-2009) who received primary systemic treatment. </li></ul></ul><ul><ul><li>AJCC stages IIB, IIIA, IIIB, IIIC and IV (with ipsilateral supraclavicular lymph node involvement only). </li></ul></ul><ul><li>Treatment Plan and Patient Evaluation </li></ul><ul><ul><li>Primary systemic treatment: </li></ul></ul><ul><ul><li>- 18 patients (56.2%) with CAF </li></ul></ul><ul><ul><li>- 2 patients (6.2) with CMF </li></ul></ul><ul><ul><li>- 1 patient (3.1%) with Taxane-based regimen (AT) </li></ul></ul><ul><ul><li>- 12 patients (34.2%) with other taxane-based regimen including Herceptin </li></ul></ul><ul><ul><li>[3 (21.9%) with TCH, 4 (6.2%) with TNH, 5 (6.2%) with AC)] </li></ul></ul>
  9. 10. <ul><li>Treatment Plan and Patient Evaluation (Continued) </li></ul><ul><ul><li>Standard surgical procedure : modified radical mastectomy. </li></ul></ul><ul><ul><li>Adjuvant radiotherapy in 24 patients (75%). </li></ul></ul><ul><ul><li>HR-positive patients received adjuvant endocrine therapy. </li></ul></ul><ul><ul><li>Follow-up: every 3 months for the first 2 years, every 6 months in the next 3 years, and annually thereafter. </li></ul></ul>
  10. 11. Patients and Methods <ul><li>Classification of Groups </li></ul><ul><ul><li>HER-2 receptor positive (HER-2 positive). </li></ul></ul><ul><ul><li>HER-2 receptor negative (HER-2 negative). </li></ul></ul><ul><ul><li>Hormonal receptor positive (ER and/or PR positive). </li></ul></ul><ul><ul><li>Hormonal receptor negative (ER and PR negative). </li></ul></ul><ul><ul><li>ER and PR status: determined on the basis of IHC staining. </li></ul></ul><ul><ul><li>HER-2 positivity: IHC 3+, or HER-2 amplification on the basis of FISH (ratio > 2.0) if IHC 2+. </li></ul></ul><ul><li>Statistical Analysis </li></ul><ul><ul><li>MedCalc software version 9.6.2.0 . </li></ul></ul><ul><ul><li>Frequency table and x 2 test to compare the distribution of baseline characteristics. </li></ul></ul><ul><ul><li>Log-rank test for comparisons between subgroups. </li></ul></ul><ul><ul><li>Kaplan-Meier method for survival analysis. </li></ul></ul><ul><ul><li>Clinical response to neoadjuvant systemic therapy: RECIST criteria. </li></ul></ul>
  11. 12. Results
  12. 13. Distribution of Patient Baseline Characteristics (n=32) 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
  13. 14. Distribution of Patient Baseline 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
  14. 15. Distribution of Patient Baseline 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
  15. 16. Patient Baseline Characteristics Stratified by Hormonal Receptor Status and HER-2 Overexpression Characterstics All patients n=32 HER-2 overexpression P Hormone receptor P Positive 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) 0.94 1(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*
  16. 17. Correlation between Patient Characteristics and Clinical 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
  17. 18. Correlation between Patient Characteristics and Clinical 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
  18. 19. Kaplan-Meier Analysis of Overall Survival Mean OS HER-2 + 36.25 months HER-2 - 41.5 months Logrank test P = 0.03 <ul><li>By HER-2 Receptor Status </li></ul>
  19. 20. Kaplan-Meier Analysis of Overall Survival Mean OS HR + 41 months HR - 36.5 months Logrank test P = 0.0009 (b) By Hormonal Receptor Status
  20. 21. Kaplan-Meier Analysis of Progression Free Survival Mean PFS HER-2 + 14 months HER-2 - 22 months Logrank test P = 0.14 (a) By HER-2 Receptor Status
  21. 22. Kaplan-Meier Analysis of Progression Free Survival (b) By Hormonal Receptor Status
  22. 23. Univariate Analysis 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 Reference 0.85 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*
  23. 24. <ul><li>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. </li></ul><ul><li>Significant association (P = 0.005) between hormonal receptor negativity and high tumor grade. </li></ul><ul><li>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). </li></ul><ul><li>This study failed to reveal any statistically significant correlation between clinical response and clinicopathological factors. </li></ul>Discussion
  24. 25. Discussion <ul><li>Significant prognostic effect of HER-2 receptor status on OS (P = 0.03, HR = 1.96, 95% CI = 1.07-5.33). </li></ul><ul><li>Significant prognostic effect of hormonal receptor status on OS (P = 0.0009, HR = 2.87, 95% CI = 1.92-12.76). </li></ul><ul><li>Significant prognostic effect of hormonal receptor status on PFS (P = 0.0027, HR = 2.52, 95% CI = 1.66-11.13). </li></ul>
  25. 26. Conclusions <ul><li>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. </li></ul><ul><li>However, no significant association with clinical response to neoadjuvant chemotherapy was found. </li></ul>
  26. 27. Breast Cancer Awareness

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