1. Breast Cancer Steven Jones, MD

2. 2 Epidemiology of Breast Cancer 182,460 American women diagnosed each year. 40,480 die each year from the disease Lifetime risk through age 85 is 1 in 8, or 12.5% 2 nd leading cause of cancer deaths among US women, after lung cancer Leading cause of death among women age 40- 55

3. 3 Mammary Gland Anterior view Lobar/Lactifero us duct Lobule Fat AmpullaNipple Areola gland Areola Lobular duct Breast Anatomy

4. 4 Lobar/Lactiferous Duct Cross Section

5. 5 The entire duct may be filled with abnormal, atypical cells. This condition is actually an early breast cancer. Ductal Carcinoma In Situ (DCIS) Lobar/Lactiferous Duct Cross Section

6. 6 Cancer cells that break out of the duct and invade the breast tissue. Invasive Ductal Carcinoma (IDC) Lobar/Lactiferous Duct Cross Section

7. 7 Breast Cancer Risks Gender – 1% male Age - < 30 – rare ; risk rises sharply after 40 Personal Hx – 0.5-1% per yr in contra breast Family Hx- 20-30% of Br Ca have + fm hx; only 5-10% have an inherited mutation

8. 8 Consider BRCA 1 / 2 testing: < 35 <50 with another positive relative < 50 Any age with 2 other positive relatives Male relative with breast cancer Jewish ancestry with young age or 1 relative

9. 9 Breast Cancer Risks Benign Breast disease – Atypical ductal hyperplasia – 4.5-5.0 RR Lobular Carcinoma in Situ – 5.4-12.0 RR, 1% per year.

10. 10 Excess growth within the duct includes abnormal or atypical cells. The presence of this condition increases the risk of developing breast cancer. Atypical Ductal Hyperplasia (ADH) Lobar/Lactiferous Duct Cross Section

11. 11 Lobular Hyperplasia Atypical Lobular Hyperplasia Excess growth in the lobules Lobular Hyperplasia Atypical lobular hyperplasia may also develop. If atypical lobular hyperplasia progresses in severity a condition referred to as Lobular Carcinoma In Situ (LCIS) may develop.

12. 12 Breast Cancer Risks Hormonal factors – early menarche, late menopause, age of 1 st pregnancy, HRT with progesterone Environment, lifestyle, and diet – ionizing radiation increase risk

13. 13 High Risk Patients Gail model Chemo prevention Increased surveillance

14. 14 Magnification Views –Improves resolution –Better determination of the shape, distribution, and number of microcalcifications –Questionable density from summation shadows will dissipate Mammography Additional Views Current status of the Digital Database for Screening Mammography," M. Heath, K.W. Bowyer, D. Kopans et al, pages 457-460 in Digital Mammography, Kluwer Academic Publishers, 1998.

15. 15 012345012345 Incomplete assessment Negative Benign finding Probably benign Suspicious Highly suggestive of malignancy Additional imaging evaluation Short interval follow-up Biopsy should be considered Appropriate action to be taken CategoryAssessment Recommendations BI-RADS ™ Report Organization

16. 16 Characteristics of imaged lesions Size Shape Border definition Internal echogenicity Posterior enhancement Architectural changes Gray scale comparison to adjacent breast tissue Breast Ultrasound

17. 17 Benign vs. Malignant

18. 18 Open Surgical Biopsy Biopsy Options  Performed in the Operating Room  An incision is made in the breast and a large tissue sample is cut and removed In some cases, a wire is inserted into the breast to aid in localizing the abnormality  Possible scarring and disfiguration that can interfere with future mammograms  More costly than other biopsy methods

19. 19 Biopsy Options  Can be performed in an outpatient setting or doctor’s office  No anesthesia  No sutures  Several needle insertions to collect fluid and/or cellular material Cyst aspiration for fluids  Unable to mark biopsy site Fine Needle Aspiration (FNA)

20. 20 Biopsy Options Core Needle Biopsy  Can be performed in an outpatient setting or doctor’s office  Local anesthesia  No sutures  4 – 6 needle insertions to collect a sufficient amount of breast tissue for an accurate diagnosis  Unable to mark biopsy site

21. 21 Cancer Cure? cut it out or burn it out

22. 22 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

23. 23 Breast Cancer Multifocality Holland 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

24. 24 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

25. 25 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.

26. 26 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%)

27. 27 Parasternal (internal thoracic) nodes Subclavian (apical axillary) nodes Interpectoral (Rotter’s) nodes Central axillary nodes Brachial (lateral axillary) nodes Subscapular (posterior axillary) nodes Pectoral (anterior axillary) nodes Mammary Gland Anterior view Breast Anatomy

28. 28 Sentinel Lymph Node Technetium labeled sulfur colloid Isosulfan blue (lymphazurin 1%) Combined – 97% ID’ed; 6% false negative 1% anaphylactic reaction to blue dye

29. 29 Systemic Therapy Cytotoxic chemotherapy Hormonal therapy – 50% reduction of recurrence, 26% reduction in mortality Targeted therapy - Herceptin – 50% reduction of recurrence.

30. 30 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 downstage to allow conversion from mastectomy to BCS

31. 31 Indications To downstage women with large tumors that cannot undergo BCS with good cosmetic result – 30% of women will downstage. Early initiation of systemic treatment In vivo assessment of response, good biological model Less radical surgery needed

32. 32 Risk of breast cancer increases with age Feuer EJ, Wun LM. DEVACN: Probability of Developing or Dying of Cancer. Version 4.0 Bethesda, MD: National Cancer Institute 1999 Facts & Figures