1. BIOLOGICAL PRINCIPLES OF BREAST CANCER TREAMENT Benjamin O. Anderson, M.D. Director, Breast Health Clinic Professor of Surgery and Global Health, University of Washington Joint Member, Fred Hutchinson Cancer Research Center Seattle, Washington

2. BIOLOGICAL BASIS OF TREATMENT Outline Breast cancer surgery Breast radiation therapy Systemic (drug) therapy

3. BIOLOGICAL BASIS OF TREATMENT Outline Breast cancer surgery Breast radiation therapy Systemic (drug) therapy

6. RADICAL MASTECTOMY MODIFIED RADICAL MASTECTOMY

7. EVOLUTION IN CANCER TREATMENT

8. BREAST CONSERVATION: Long-term validation

9. NSABP B-06: Effect of Lumpectomy v. Mastectomy on Recurrence CUMULATIVE INCIDENCE All Patients Node NegativeNode Positive Lumpectomy Lumpectomy + radiation Lumpectomy: 570/210361/121209/89 Lumpectomy + XRT:567/62375/50192/12 No. of patients / No. of recurrences YEAR

10. NSABP B-06: Effect of Lumpectomy v. Mastectomy on Survival DISTANT DISEASE-FREE SURVIVAL (%) Cohort A Cohort BCohort C Total Mastectomy: 692/265569/233494/192 Lumpectomy:699/302634/282520/236 No. of patients / No. of recurrences YEAR Lumpectomy + XRT:714/278628/253515/204

12. SURGICAL MARGINS: Surgical Principles Cancers must be removed with NEGATIVE MARGINS for adequate local treatment Some cancers can be removed with negative margins with a partial mastectomy Other cancers require mastectomy for complete removal with negative margins

13. BIOLOGICAL BASIS OF TREATMENT Outline Breast cancer surgery Breast radiation therapy Systemic (drug) therapy

14. BIOLOGICAL BASIS OF TREATMENT Outline Breast cancer surgery Breast radiation therapy Systemic (drug) therapy

15. BREAST CONSERVING SURGERY

16. BREAST CONSERVING RADIATION THERAPY

17. BREAST CONSERVATION: Radiation Therapy Concepts Surgical lumpectomy: removes tumor bulk Radiation therapy after surgery: eradicates residual microscopic cancer POSTOPERATIVE RADIATION TREATMENT DECREASES LOCAL RECURRENCE RISK OF BREAST CANCER FROM 30-40% to 10%

18. BIOLOGICAL BASIS OF TREATMENT Outline Breast cancer surgery Breast radiation therapy Systemic (drug) therapy

19. BIOLOGICAL BASIS OF TREATMENT Outline Breast cancer surgery Breast radiation therapy Systemic (drug) therapy

22. AXILLARY NODE DISSECTION: Complication Rates Lymphedema – Acute: 40% – Chronic: 15-20% Paraesthesia: 40% Need for a drain: 100% Seroma formation: 10%

23. SENTINEL NODE CONCEPT

24. BREAST CANCER TREATMENT: Adjuvant Systemic Therapy Chemotherapy or hormonal therapy used after operation Improves survival rates beyond operation alone Used for node-positive and some node- negative invasive cancers

26. NEOADJUVANT CHEMOTHERAPY: Definition Preoperative systemic chemotherapy intentionally administered prior to definitive surgical resection

27. NEOADJUVANT CHEMOTHERAPY: NSABP B-18 - Operable 1,523 randomized: AC / preop vs. postop No difference in DFS or OS at 5 years cCR / m CR / pCR correlated with outcome Increased Lumpectomy / XRT after NCT (67.8% vs 59.8%, p < 0.05) Similar local recurrence after lumpectomy (7.9% vs 5.8%, p =.23) Fisher, J Clin Oncol 16:2672, 1998

28. NEOADJUVANT THERAPY NEOADJUVANT THERAPY Categories of Breast Cancer Inflammatory breast cancer – Stage III B Locally advanced breast cancer – Stage III non-inflammatory: – T3 / clinN1-2 “Operable” breast cancer – Stage II B: T3N0, T2 (borderline BCT)

29. NEOADJUVANT THERAPY NEOADJUVANT THERAPY Rationale Inflammatory breast cancer – Convert inoperable to marginally operable Locally advanced breast cancer – Convert marginally operable to resectable “Operable” breast cancer – Improve breast conservation rates

30. PRIMARY NEOADJUVANT RESPONSE PRIMARY NEOADJUVANT RESPONSE Utility of Breast MRI for Following Drug Response Partridge AJR 2005;184:1774 Pre-treatment – 22 cm 3 One Cycle 30% Decrease Four Cycles 88% decrease

31. CONCLUSIONS Breast surgery removes the primary disease in the breast and provides staging information to determine adjuvant treatment. Radiation therapy allows for conservation of the breast (as opposed to mastectomy) in properly selected patients. Systemic (drug) treatment is critical for improving mortality and is not replaced by more extensive local therapy. Multidisciplinary collaboration is the heart and soul of breast cancer treatment and is required to improve patient outcome.

32. UNIVERSITY OF WASHINGTON FRED HUTCHINSON CANCER CENTER CHILDREN’S HOSPITAL SEATTLE CANCER CARE ALLIANCE UNIVERSITY OF WASHINGTON FRED HUTCHINSON CANCER CENTER