Local Management of Invasive Breast Cancer

1. Local Management of Invasive Breast Cancer By Steven Jones, MD

2. Connecting with the patient is the best part of medicine. We’re artists, not engineers

7. Epidemiology of Breast Cancer • 232,340 American women diagnosed each year. • 39,620 die each year from the disease • Lifetime risk through age 85 is 1 in 8, or 12.5% • 2nd leading cause of cancer deaths among US women, after lung cancer • Leading cause of death among women age 40-55

8. Staging Recommendation prior to primary therapy • History and physical • Liver function tests • Breast imaging: ipsilateral and contralateral breasts • Mammogram • U/S • MRI • Axillary imaging • U/S • MRI

9. MRI for Local-regional Staging Pros: Cons: With adjuvant therapy local failure low – 6% Too many mastectomies Some data demonstrate no difference in local failure rates • Changes surgery 20% • Multifocal- 3.6% • Multicentric – 4.4% • Contralateral – 1.8%

10. MRI Pre-op • Diagnostic dilemma • BRCA 1 / 2 known or suspected carriers wishing BCT • Occult malignancy presenting with axillary mets

11. Staging Recommendation Prior to Primary Therapy

12. CRITERIA FOR REFERRAL FOR GENETIC COUNSELING OF INDIVIDUALS AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST CANCERa,b • Personal history of breast cancer diagnosed≤ 40 • Personal history of breast cancer diagnosed≤ 50 and Ashkenazi Jewish ancestry • Personal history of breast cancer diagnosed≤ 50 and at least one first- or second-degree relative with breast cancer ≤50and/or epithelial ovarian cancer aClose relatives of individuals with the history mentioned in the table are appropriate candidates for genetic counseling. It is optimal to initiate testing in an individual with breast or ovarian cancer prior to testing at-risk relatives. bCriteria modified from NCCN (109)

13. Continued…. • Personal history of breast cancer and two or more relatives on the same side of the family with breast cancer and/or epithelial ovarian cancer • Personal history of epithelial ovarian cancer, diagnosed at any age, particularly if Ashkenazi Jewish • Personal history of male breast cancer particularly if at least one first- or second-degree relative with breast cancer and/or epithelial ovarian cancer • Relatives of individuals with a deleterious BRCA1/2mutation

14. Evolution of Breast Cancer “Cancer of the breast spreads centrifugally. It disseminates to bone by way of the lymphatics, not by blood vessels.” Halsted, WS. The results of radical operations for the cure of carcinoma of the breast. Ann Surg 1907; 66:1

15. Halstedian concept did not apply More extensive surgical procedures did not reduce risk of distant metastasis Identification of small breast cancer by mammography

16. National Surgical Adjuvant Breast Project • Radical mastectomy vs • Simple mastectomy with axillary irradiation vs • Simple mastectomy with delayed axillary dissection Started in 1971, 1665 patients enrolled, 25 year follow up No difference in disease free or overall survival

17. Breast Cancer MultifocalityHolland et al. • Only 37% of cancers are confined to the primary tumor. • 20% have additional cancer within 2 cms. • 43% have additional cancer beyond 2 cms. Holland R, Veling S, Mravunac M, et al. Histologic multifocality of Tis, T1-2 breast carcinomas: implications for clinical trials of breast-conserving treatment. Cancer 1985; 56: 979

18. NSABP B-06 • Total mastectomy vs lumpectomy vs lumpectomy plus irradiation • No significant difference in survival • 14.3% recurrence in lumpectomy plus radiation group at 25 years • 39.2% recurrence in lumpectomy without radiation group at 25 years

19. Conclusion NSABP B-06 • Lumpectomy followed by breast irradiation is the appropriate therapy for women with breast cancer, provided that the margins of resected specimens are free of tumor and an acceptable cosmetic result can be obtained.

20. Contraindications for Breast Conserving Therapy • Absolute: • Prior radiation to the breast or chest wall • Pregnancy • Muticentric disease • Diffuse, malignant appearing microcalcifications

21. Relative Contraindications for BCT • History of collagen vascular disease • Very large tumor > 5cms • Very large breasts

22. Margins • Clear: tumor not touching the ink • Close: < 1mm – may be a problem with young or extensive intraductal component

23. ALGORITHM FOR ADJUVANT SYSTEMIC THERAPY FOR BREAST CANCER ER, estrogen receptor; PR, progesterone receptor aFormerly HER-2

24. Radiation Therapy • Whole breast with boost to tumor bed standard • Accelerated partial breast irradiation • Balloon ( Mammosite) • Interstitial brachytherapy • External beam limited RT • Intraoperative limited RT

25. Post-mastectomy Radiation • Early studies showed increased mortality • Recent studies show substantial decrease in locoregional recurrence • Recent trials show survival benefit 5-8% at > 10 years.

26. Indications for Post-mastectomy Radiation • T3 or T4 tumors • Tumors invading skin or muscle • 4 or more pos. axillary nodes • (Some recommend for 1-3 nodes, depending)

27. Breast Reconstruction • Immediate – skin sparing • Delayed immediate – skin sparing • Delayed

28. Skin Sparing Mastectomy Includes areolar (nipple sparing controversial) Excise biopsy incision Radiate positive margins

29. Axillary Biopsy and Control 1. Staging • In the absence of distant mets number of positive lymph nodes is the most important prognostic factor. 2. Regional Control In clinically negative axilla, axillary dissection reduces local occurrence from 20% to 3% 3. Small survival advantage (3-5%)

30. Sentinel Lymph Node • Technetium labeled sulfur colloid • Isosulfan blue (lymphazurin 1%) • Combined – 97% ID’ed; 6% false negative • 1% anaphylactic reaction to blue dye

31. Locally Advanced Cancer • Large primary tumors (>5cm) especially with pos. nodes • Tumors with skin or chest wall involvement • Tumors with fixed or matted axillary nodes or ipsilateralsubclavian or supraclavicular lymph nodes • Most have been present for months or years but treatment has been delayed

32. Inflammatory Breast Cancer • Rapid onset and progression over weeks to months • Skin often discolored red to purple • Skin thickened or peau d’ orange • Induration • Invasion of dermal lymphatics is a common feature but not required or sufficient for a diagnosis • 1-5% of breast cancers

33. NeoadjuvantChemotherapy aka Preoperative Systemic Therapy aka Primary Chemotherapy

34. NSABP B-18 • Started 1988; 1523 pts, 4 cycles AC • 80% overall response • 13% pathologic complete response • No difference in overall survival • Only 3% had progression of disease • 25% downstaging at axilla • 30% of women will downsize to allow conversion from mastectomy to BCS

35. Indications • To downsize women with large tumors that cannot undergo BCS with good cosmetic result – 30% of women will downsize. • Early initiation of systemic treatment • In vivo assessment of response, good biological model • Less radical surgery needed

36. Pre-operative Endocrine Therapy • Best for large low grade ER pos. tumors in post menopausal women • Response times 3 months or longer • Greater response with aromatase inhibitors compared with tamoxifen • Under-utilized in the US

37. Tulane surgery:“ tough as the marines except the marines get to eat”