1. BREAST CANCER 101 BREAST CANCER 101 A REVIEW OF PROBLEMS, DIAGNOSTICS, AND CLINICAL MANAGEMENT Sabha Ganai, MD, PhD Assistant Professor of Surgery Southern Illinois University School of Medicine

2. DISCLOSURES My conflicts of interest are relevant to being a practicing surgical oncologist.

3. Objectives Provide an overview of trends in breast cancer incidence and mortality Review screening and diagnostic modalities important for management of breast cancer Discuss therapeutic approches for breast cancers

4. Breast Cancer 1 in 8 (12.3%) lifetime risk for US women –Increased from 1 in 11 in the 1970s. CA Clin J 2014; 64: 52-62.

5. CA Clin J 2014; 64: 9-29.

8. Breast Cancer Incidence CA Clin J 2014; 64: 9-29.

9. Breast Cancer Mortality

10. Breast Cancer Mortality has declined by 34% since 1990.

11. Incidence and Mortality CA Clin J 2014; 64: 52-62.

12. Incidence and Mortality CA Clin J 2014; 64: 52-62.

13. ACS Screening CA Clin J 2014; 64: 52-62.

14. The Controversy… What are the harms of mammography? –overdiagnosis? –more anxiety? –more biopsies? –time/days off work? –more cost?

15. USPSTF (2009) Biennial Mammography ages 50-74 “The decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take into account patient context, including the patient’s values regarding specific benefits and harms.”

16. Mortality Reduction 71% survival benefit following ACS screening guidelines beyond 23% mortality reduction achieved following USPSTF guidelines Additional 5 lives saved per 1000 women.

17. Potential Harms Call backs for additional imaging (anxiety) False-positive biopsies False-negative screen –Missed breast cancer (dense breasts) Radiation-induced breast cancer risk Over-diagnosis –detection of a cancer that might not otherwise become clinically-apparent during screen

18. Potential Harms

19. Screening women in 40s: –False-positive mammogram once every 10y –False-positive biopsy once every 149y Invitation to treat women in 40s in Swedish mammography studies led to 29% reduction in breast cancer mortality over 16 years

20. Annual vs. Biennual Screening –Annual screening leads to 30% lower recall rates, detection of smaller tumors, and impact on stage migration Screening ages 40 to 79 is more cost- effective than seat belts and airbags with regard to cost-per-life-year gained –Better than drug development

21. Adherence and compliance behaviors –If women’s screening behaviors are established earlier, adherence to screening mammography improves over time. –Women respond to an endorsement of guidelines. Strategy to leave decision-making up in air does not educate on risk stratification for breast cancer

22. Screening Breast MRI CA Clin J 2007; 57: 75-89.

23. Screening Breast MRI CA Clin J 2007; 57: 75-89.

24. Screening Breast MRI CA Clin J 2007; 57: 75-89. Should be limited to centers with biopsy capabilities

25. Genetic Counseling Referral Early-onset breast cancer (<50y) Triple-negative breast cancer (<60y) Two breast primaries or breast and ovarian cancer Two or more close blood relatives with breast cancer Male breast cancer Pancreas cancer Clustering of other cancers

26. Genetic Testing Hereditary Breast and Ovarian Cancer Syndrome –BRCA1 60-80% lifetime risk breast cancer 20-40% lifetime risk ovarian cancer –BRCA2 40-60% lifetime risk breast cancer (5-10% male) 10-20% lifetime risk ovarian cancer Pancreas and prostate cancer

27. Genetic Testing PTEN (Cowden’s Disease) 25-50% lifetime risk breast cancer Thyroid, endometrial, genitourinary cancers p53 (Li-Fraumeni Syndrome) >90% lifetime risk breast cancer Sarcomas, brain tumors, adrenocortical tumors, colorctal cancers CDH1 40% lifetime risk breast cancer (lobular) Hereditary diffuse gastric cancer

28. Molecular Subtyping

29. Breast Cancer Biology ER PR HER2 Basal-like (Triple negative) HER2 Luminal (ER+)

30. Molecular Subtyping Luminal (Hormone-Receptor+) –Responsive to tamoxifen and aromatase inhibitors HER2 –Responsive to trastuzumab and newer biologic therapies Basal-like (“Triple-negative”)

31. Triple Assessment Clinical Exam –H&P Imaging –Diagnostic mammography / ultrasound Pathology –Core needle biopsy

32. Biopsy Stereotactic Core Needle Biopsy Ultrasound-guided Core Needle Biopsy –If Cancer, should get ER/PR/HER2 IHC Surgical (Excisional) Biopsy –Non-concordant results –Atypia on a core biopsy Sampling error (10-20%) –Papillary lesions, radial scars

33. Surgical Management in 1900s William Stewart Halsted Halsted Mastectomy –Radical extirpation of breast with pectoralis and lymph nodes Predicated on notion that breast cancer spreads locally and regionally via lymphatics

34. Paradigm Shift Bernard Fisher –1967 – Chairman of National Surgical Adjuvant Breast and Bowel Project (NSABP)

35. Paradigm Shift Bernard Fisher –“because operable breast cancer is a systemic disease involving a complex spectrum of host-tumor interrelations, local-regional therapy is unlikely to affect survival.”

36. “Before 1971, if you had breast cancer, chances are you’d have to get your breast cut off. Surgeons had been taught one thing: radical surgery saves lives. It was Bernard Fisher who changed their minds, getting reluctant breast surgeons to enter their cancer patients into clinical trials that tested less aggressive surgery against the Halsted radical mastectomy. ”

37. NSABP B-04

38. NSABP B-06

39. Lowdown Breast-conserving therapy (lumpectomy + whole-breast radiation) and Mastectomy have similar overall survival benefit –Includes Triple-negative cancers –Goal is “clear-at-ink” negative margins 2014 SSO/ASTRO guidelines Mastectomy should be paired with referral to a Plastics/Reconstructive Surgeon

40. Oncoplastic Techniques Mastectomy –Nipple-sparing and Areola-sparing skin-sparing approaches Partial Mastectomy –Various approaches accounting for location, volume and aesthetic considerations

41. What about the Axilla?

42. Axillary Complications

44. ACOSOG Z0011 Only applies to cT1-2N0 patients undergoing breast conserving surgery with radiotherapy –Observation is acceptable for SLN+ patients If SLN+ after mastectomy, Axillary Lymph Node Dissection is still recommended

47. OncotypeDX 21-gene RT-PCR recurrence score Performed on paraffin-embedded specimens Developed and validated on patient tumor blocks from NSABP B-14 (TAM vs. Obs) and B-20 (TAM vs. Chemo/TAM)

49. Hormonal Tx

51. Add Chemo

52. The Future Neoadjuvant Clinical Trials –Chemo before surgery –Assessment of response to therapy Evolving role of surgical management of axilla –Bigger surgery does not cure bad biology Optimal screening paradigm in context of better imaging strategies and therapies will need to be determined –An individualized approach?

53. Questions?