1. BREAST CANCER B.KLEIN ONCOLOGY MEIR HOSPITAL

3. CASE REPORT 40 Yrs old woman felt a lump in her left breast Px : 3x2cm mass in LUQ moveable. No LN palpated She underwent L lumpectomy +LN dissection Pathology:G3 IDC+20% DCIS, T=2.5 cm N=2+/15, vascular invasion. ER= 0%, PR= O% HER-2 +++(HIC)

4. Parkin et al. Eur J Cancer. 2001;37:S4. Fisher et al. J Natl Cancer Inst Monographs. 2001;30:62. *American Joint Committee on Cancer. Handbook for Staging of Cancer; 1993. Breast Cancer Worldwide estimates for 2001 –1,050,000 new cases –370,000 breast cancer–related deaths Second leading cause of cancer death in women Outcome is directly related to stage at diagnosis, eg, survival after 5 years* –Stage I disease95% –Stage II disease 70%-85% –Stage III disease50%-52% –Stage IV disease 17%

5. Case report cont. The pat. Comes to you What is important in the history? Menopausal status Hormone use Family history Relevant past history

7. Ductal carcinoma in situ

8. Infiltrating lobular carcinoma A normal duct (yellow arrow) is the center of cells arranged in concentric circles (white arrows). This “target pattern” is classic!

11. BREAST CANCER Anatomical site RIGHT Upper inner Nipple Central portion Lower inner Upper outer Axillary tail Lower outer

14. BREAST CANCER Stage IIB T3 N0 M0 N1 = metastasis to movable ipsilateral axillary lymph node(s) (p) N1a, N1b M0 = no distant metastasis T > 5 cm T2 N1 M0 T3

15. BREAST CANCER Stage IIIA T0T1T2T3 Metastasis to ipsilateral axillary lymph node(s) N1 = movable N2 = fixed to one another or to other structures M0 = no distant metastasis T3 N1 M0 N2 M0

16. BREAST CANCER Stage IIIB Any T N3 M0 N3 = metastasis to ipsilateral internal mammary lymph node(s) M0 = no distant metastasis Tumor of any size with direct extension to chest wall or skin T4d = inflammatory carcinoma T4 any N M0 T4

18. BREAST CANCER Commonly assessed prognostic factors Slamon DJ. Chemotherapy Foundation. 1999;46. Winer E, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;1651-1717. Nuclear grade Estrogen/progesterone receptors HER2/neu overexpression Number of positive axillary nodes Tumor size Lymphatic and vascular invasion Histologic tumor type Histologic grade

19. BREAST CANCER Incidence of major histologic types Percent of all invasive carcinomas Hendersn IC. American Cancer Society Textbook & Clinical Oncology. 2nd ed. 1995;198-219. 80% 10% 5% Infiltrating Lobular Medullary

20. BREAST CANCER Spread to lymph nodes Supraclavicular Subclavicular Distal (upper) axillary Central (middle) axillary Proximal (lower) axillary Mediastinal Internal mammary Interpectoral (Rotter’s)

21. BREAST CANCER 5-year survival as function of the number of positive axillary lymph nodes 0% 20% 40% 60% 80% 5-Year Survival 0123456-1011-1516-20>20 Number of Positive Nodes Harris J, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;1557-1616.

23. Total mastectomy Lumpectomy only Lumpectomy + RT 23 Lumpectomy and axillary dissection plus radiation therapy will reduce local recurrence, and although RT it does’t affect survival, this therapeutic module is incorporated into the adjuvant therapy. Lumpectomy and axillary dissection plus radiation therapy should be part of the standard adjuvant therapy for breast cancer.

24. Definitions Early breast cancer Locally advanced breast cancer Metastatic breast cancer Breast cancer that is limited to the breast and axilla Tumors larger than 5cm with adjacent structures involvement or inflammatory carcinoma Tumors in supraclavicular area and beyond 24

25. סוגי טיפול טיפול אג'ובנטי (טיפול משלים, מסייע) טיפול לאחר\ניתוח כאשר אין כל סימני מחלה. המטרה: לחסל את המיקרומטסטזות טיפול ניאואגובנטי ניתן לפני הניתוח בכדי להקטין את הגידולולעשות אותו נתיח. לאתמיד הגידול בלתי נתיח

26. Historical Perspective of Adjuvant Treatment of Breast Cancer Breast cancer treated as locoregional disease Treatment = surgical approach Animal tumor models = breast cancer a systemic disease Surgery + monotherapy ( Nissen-Meyer ) Trials evaluating systemic therapy with less aggressive surgery (Veronesi)…establishing CMF (Bonadonna) Growth kinetics and trials support adjuvant therapy Trials with adjuvant CT – role of AC as U.S. standard regimen PolyCT, tamoxifen, and polyCT + tam: efficacy debated Oxford overview analyses Novel agents: taxanes, Herceptin Biological predictive and prognostic factors 50’s 60’s 70’s 80’s 90’s BCIRG JUNE 23, 2002

27. 1995 Adjuvant Oxford Overview Relative % Decrease in Mortality TamChemoCombined <50 y ER+25%25%45% ER- 0%35%-- >50 y ER+25%10%35% ER- 0%20%-- BCIRG JUNE 23, 2002

28. Comparative Efficacy of Adjuvant Chemotherapy: EBCTCG Meta-Analyses Therapy Reduction in Annual Odds, % RecurrenceDeath Polychemotherapy vs23.515 no chemotherapy (1995)(P <.00001)(P <.00001) Anthracyclines vs1211 CMF (1995)(P =.006)(P =.02) Anthracyclines vs10.815.7 CMF (2000)(P =.0005)(P <.00001) BCIRG JUNE 23, 2002

29. Actuarial estimate and SE: A/E regimen CMF years 2000 Oxford Overview Analysis A/E Regimen vs CMF: Recurrences 70.9% 68.4% 2.6% (SE 0.9) % 57.9% 3.5% (SE 1.2) 61.4% BCIRG JUNE 23, 2002

30. Anthracycline-Based Treatment  Anthracycline-based regimens (epirubicin or doxorubicin) compared to those without anthracyclines: –4 cycles of EC or AC equivalent to 6 cycles of CMF –more intense anthracycline-based regimens with  3 drugs (CEF/FEC/CAF) superior to CMF BCIRG JUNE 23, 2002

31. Henderson et al., J Clin Oncol 2003; 6: 1–9 Adjuvant paclitaxel None 3170 patients with (+) nodes Median f/u 18 months 3170 patients with (+) nodes Median f/u 18 months (60 vs 75 vs 90) P 175 mg/m 2 (3h) C C A A CALGB 9344 / Intergroup 0148

32. No paclitaxeln = 1551Events = 563Median = NAChi-square = 9.72 Paclitaxeln = 1570Events = 491Median = NAp-value = 0.0018 No paclitaxeln = 1551Events = 563Median = NAChi-square = 9.72 Paclitaxeln = 1570Events = 491Median = NAp-value = 0.0018 Disease-free survival CALGB 9344 By treatment arm 0 0 0.2 0.4 0.6 0.8 1.0 0 0 2 2 4 4 6 6 Years from study entry Proportion disease-free No paclitaxel Paclitaxel Henderson et al., J Clin Oncol 2003; 21(b): 1–9

33. Receptor-positive tumors CALGB 9344 Disease-free survival: Exploratory analysis 0 0 0.2 0.4 0.6 0.8 1.0 0 0 2 2 4 4 6 6 Proportion disease-free Years from study entry No paclitaxel Paclitaxel Henderson et al., J Clin Oncol 2003; 21(b): 1–9

34. Years from study entry Receptor-negative tumors CALGB 9344 Disease-free survival: Exploratory analysis 0 0 0.2 0.4 0.6 0.8 1.0 0 0 2 2 4 4 6 6 Proportion disease-free No paclitaxel Paclitaxel Henderson et al., J Clin Oncol 2003; 21(b): 1–9

39. סיכום טיפול חולות פרה מנופאו. בלוטות חיוביות :כימוטרפיה. אם רצפטורים חיוביים להוסיף טמוקסיפן או בלוטות שליליות:כימו או הורמונו. חולות פוסטמנופאו. בלוטות חיוביות רצפטורים חיוביים אפשר להסתפק בהורמונים אפשר גם כימו תלוי ברמת החיוביות. חשיבות רבה לher-2