Managing Breast Abnormalities in the Primary Care Practice

1. Managing Breast Abnormalities in the Primary Care Practice Benjamin D. Li, MD, FACS Charles Knight Sr. Professor and Vice Chairman Department of Surgery Chief, Surgical Oncology LSUHSC-Shreveport and the Feist-Weiller Cancer Center

2. Outline - 1 • Clinical presentations of breast disease • Nipple discharge • Mastalgia • Breast mass • diagnostic imaging • who to biopsy • how to biopsy

3. Outline – 2 • Treatment of breast cancer • Local-regional control of breast cancer • Surgery • Modified Radical Mastectomy (MRM) • Breast Conservation Therapy (BCT) • Addressing nodal disease • Axillary Lymph Node Dissection (ALND) • Sentinel Lymph Node Biopsy (SLNB) • Radiation therapy • Postmastectomy Radiotherapy (PMRT) • Whole breast irradiation versus Accelerated Partial Breast Irradiation (APBI)

4. Outline - 3 • Systemic adjuvant therapy • Advances in chemotherapy • Taxanes • Dose dense regimens • Evolving paradigms in hormonal manipulation • Estrogen receptor inhibition • Aromatase inhibitors

5. Outline - 4 • Breast cancer screening • Guidelines for screening • Risk Factors for breast cancer • Family history • Low relative risk • High relative risk • BRCA genes • Who should be tested • Breast cancer risk reduction • Prophylatic surgery • Chemoprevention

6. Clinical Presentation • 3 most common breast complaints: • Mastalgia • NIPPLE DISCHARGE • MASS • >50% of patients presenting to surgeon with a breast condition will have benign disease Marchant, Surg Oncol Clinics of North America, 1998

7. Caution! • Applying the correct diagnostic and/or therapeutic algorithm is critical • Treat patient thoughtfully – • Look for a mass • Image area as appropriate • Ultrasound • Mammogram • Balance the need for diagnostic workup and avoid unnecessary procedure(s)

8. Breast Pain (Mastalgia) • Almost all women will have experienced varying degree of breast pain in her lifetime ranging • mild discomfort • severe pain • cyclical • estrogen overstimulation • methylxanthines

9. Mastalgia • Mastalgia is a poor predictor for cancer risk • <5% of breast cancer are associated with pain • >95% of patients with some breast pain • Beware! • Though the association of breast pain and breast cancer is NOT strong, the fear is very REAL

10. Management of Mastalgia • The most important questions: • Is there a dominant mass? • Physical examination for dominant mass • Follow the workup of a breast mass • Is there associated nipple discharge? • If there is bloody or serous discharge, follow nipple discharge workup • Does patient have recent breast imaging • Mammogram • Ultrasound • If abnormal, follow workup of a breast mass

11. Management of Mastalgia • If the breast examination and mammograms are negative: • Discontinue caffeinated products • Discontinue nicotine use • Nonsteroidal anti-inflammatory agents (NSAIDs) • Hormonal manipulation • Danazol • 6 month trial of 100 to 400mg daily • Side effects • Tamoxifen • Vitamins • A and E • Repeat examination in 4 to 6 months

12. Nipple Discharge • Less than 5% chance of cancer Leis, World J Surgery, 1999 • Differentiate between high versus low risk by history Higher risk Lower risk Spontaneous versus provoked Unilateral versus bilateral Bloody/serous versus cloudy and/or multicolored Post- versus pre-menopasual

13. Nipple Discharge • Physical examination • Is there a subareolar mass? • Types of imaging • Mammogram • Ultrasound • Duct ectasia • Ductogram • Intraductal defect

14. Nipple Discharge • Determine the need for histologic diagnosis based on the following • History • Examination • Imaging • Causes of nipple discharge • Most common cause for spontaneous nipple discharge is intraductal papiloma • BUT intraductal (DCIS) and invasive ductal carcinoma can cause nipple discharge (5%)

15. Management of a Breast Mass • Questions that need to be addressed • Is it dominant? • What is the age of patient? • How long has it been? • Has it change in size? • Any associated symptoms? • discharge • skin changes • pain • What is the relative risk for cancer? • previous biopsy • family history

16. Management of a Breast Mass • Determine the type of imaging • Diagnostic mammogram • Reserved for older than 30 years of age • Pleomorphic microcalcification • Architectural distortion • Ultrasound • Diagnostic imaging • Cystic versus solid • NOT a screening test – nonspecific • MRI • Dense breast tissue • Post radiation therapy • PET scan • In house protocol for recurrent disease

17. Management of a Breast Mass • Determine if histologic confirmation is necessary • Cystic lesion • Simple versus complex • Is there any intra-cystic defect? • Does it need drainage? • Solid lesion • Mammographic criteria • BiRads • Suspicious ultrasound characteristics • Solid lesion with • Low level internal echo • Irregular margin • Taller than in it is wide

18. Management of a Breast Mass • 2 categories of biopsy • Excisional • Removes the whole lesion • Incisional • Removes part of the lesion

19. Excisional Biopsy • Often used for palpable lesion • Nonpalpable, mammographically detected lesion • Needle localization • Blue dye injection • Benefits • Removes lesion completely • Reduces risk for sampling error • If tumor-free margin is achieved • Lumpectomy with curative intent

20. Incisional Biopsy • By definition, samples the lesion • Fine needle aspiration (FNA) • Cytology • Open wedge biopsy • Tru-cut or core biopsy • Image guided or by palpation • Mammogram • Stereotatic core biopsy (SCB) • Mammotomy • Ultrasound

21. Treatment for Breast Cancer

22. Breast Cancer Outcome • Incidence 211,240 • Death 40,410 • 5 yr survival 1975 75% 1986 78% 2000 88% Jemal, et al., CA Cancer J Clin 55(1);10, 2005 • Improvement in breast cancer outcome • Early detection • Multimodal therapy • Locoregional control • Systemic adjuvant therapy

23. Breast Cancer Therapy • Local-regional control • Surgery • Radiation therapy (XRT) • Systemic control • Chemotherapy • Hormonal manipulation

24. Surgical Therapy for Breast Cancer“The Gold Standard” • Modified Radical Mastectomy (MRM) • Total mastectomy • Removal of all gross breast tissue • including the nipple areolar complex • Level I and II axillary node dissection (ALND) • Breast Conservation Therapy (BCT) • Excision of cancer with tumor-free margin • lumpectomy • ALND • XRT

25. Systemic Therapy • Adjuvant therapy based weighing • Risk of recurrence • Sequelae of therapy • Chemotherapy • Node-positive patients • Tumors >1 cm • Age/Menopausal status • Overall health of patient • Endocrine therapy • Receptor status (ER and PR) • Anti-estrogen • Aromatase inhibitors (AIs)

26. Breast Conservation Therapy • Removal of breast cancer • Lumpectomy • Quadrantectomy • Partial mastectomy • Segmentectomy • Must achieve tumor-free margins • Axillary node dissection • Breast irradiation • 4500 to 5000 cGy • 5 to 6weeks • Whole breast irradiation

27. What to do with the lymph nodes?

28. Management of Axillary Lymph Nodes • Infitrating ductal cell carcinoma (IDCA) • Invasion of tumor cells beyond the basement membrane • Nodal basin needs evaluation • Gold Standard • Complete ALND • Sentinel Node Biopsy (SLNB) • Early breast cancer

29. Axillary Node Dissection • Staging: • Single best predictor for risk of systemic disease and cancer recurrence • Therapeutic decisions • Systemic therapy • Radiation therapy • May improve survival and cuure

30. NSABP B-06 20 Year Update • Randomized trial initiated in 1976 • 3 arms (all patients underwent ALND) • Total mastectomy (MRM) • Lumpectomy • Lumpectomy and XRT (BCT) • Accrued 2,163 patients with tumors • < 4 cm • Included node- positive and negative patients • Establishes the efficacy and safety for BCT Fisher, NEJM Oct., 2002

31. Breast Conservation Versus Mastectomy • For most women, breast conservation therapy is as good as mastectomy • Contraindications remain • Multicentric disease • Inability to obtain negative margins • Breast lesion and breast size • Contraindication to radiation therapy • Patients’ preference • Compliance

32. Evolving Treatment Paradigms:The Sentinel Node

33. Sentinel Lymph Node Biopsy (SLNB) • Definition • “gate-keeper” or first echelon node to drain a tumor, i.e. primary breast cancer • Focuses on • Identify node-negative patients • avoid unnecessary node dissection • Identify node-positive patients • Complete node dissection • Systemic therapy • XRT

34. Identifying the Sentinel Node • Injection material • Technetium-99m sulfur colloid • Isosulfan blue • Site of injection • Intra-tumoral • Intra-parenchymal • Intra-dermal/peri-areolar • Embryological: axilla • May miss internal mammary nodes

35. Potential Benefits • Risk reduction for lymphedema • Group 1: 117 patients SLNB and node dissection • Group 2: 303 patients SLNB without node dissection • Lymphedema 17.1% versus 3% (p<0.0001) Sener, Cancer, 2001 • Higher degree of scrutiny of SLN by pathologists • Cursory examination of 10 to 25 nodes • Extensive evaluation of a few nodes • Application of molecular techniques

36. Potential Risks • Risk of not finding the sentinel node: 5% • In clinical trials after training • Higher in early part of learning curve • FALSE negative rate (FNS): 5 to 10% • Technical error • Injection site • Type of contrast used • Learning curve • Alternate lymphatic drainage

37. Risks of False Negative SLN • Implications for the patients • Leaving behind nodal disease • Local-regional recurrence • Systemic implications • Understaging of disease will lead to under-treatment • Small tumor, node-negative disease • Impacts choice of adjuvant • Chemo regimen • Postoperative axillary XRT

38. False Negative SLN • To reduce the number of missed node-positive patients: • Select patients with less likelihood of node-positive disease • Practical application based on 1,000 patients • FNR = 5% • Applied to a 10% node-positive risk group • You will miss 5 node-positive patients • Applied to a 40% node-positive risk group • You will miss 20 node-positive patients

39. Critical Issues with SLN Biopsy • Technical competence • Learning curve • Mapping accuracy • Blue dye plus Tc-sulfur colloid • Maintain quality control • False negative rate must be 5% or less • Validated by performing completion ALND in the initial experience • Surveillance of patients for cancer recurrence

40. Critical Issues with SLN Biopsy • NO SURVIVAL DATA • NSABP trial • ACOSOG Z00010 and Z00011 • Await cancer cooperative groups results • Importance of Informed Consent

41. Is SLNB Safe? • Prospective, randomized trial in Milan • Over 250 patients in each arm • SLNB with completion ALND versus SLNB alone (if SLNB is negative) • In the SLNB followed by ALND • Accuracy = 96.9% • False negative rate = 8.8% • SLNB alone group (median follow-up = 46 months) • No overt axillary metastasis • No difference in rate of cancer events • 16.4 per 1,000 per year in ALND • 10.1 per 1,000 per year in SLNB Veronesi, et al., NEJM, 2003.

42. Take Home Message • ALND remains the gold standard • Quality control • Careful patient selection for SLNB alone • T1 and small T2 lesion • Unicentric lesion • Avoid patients with excisional breast biopsy > 6 cm • Avoid patients treated with neoadjuvant therapy • Avoid patients with previous axilla surgery • Avoid patients with gross nodal disease Anderson, JNCCN, 2003.

43. Evolving Treatment Paradigms: Adjuvant Radiation Therapy • Accelerated Partial Breast Irradiation (APBI) • Postmastectomy radiotherapy (PMRT)

44. Postoperative XRT after BCT • External Beam Radiation Therapy (EBRT) • Whole breast therapy • Daily treatment for 5 to 6 weeks • Total dosage: 5000 cGy • Compliance issue • Non-compliance: 50% • Local failure: 50% Li, Ann Surg, 1999

45. Accelerated Partial Breast Irradiation (APBI) • Limit the volume of breast to be treated • Within 2 cm border of lumpectomy • XRT completed in 4 to 5 days after lumpectomy • Multicatheter interstitial brachytherapy • Balloon catheter brachytherapy (MammoSite) • 3-D conformal external beam radiotherapy • Intraoperative radiotherapy

46. Summary of APBI Results • Multicatheter interstitial brachytherapy • Longest follow-up (median FU 27 to 91 months) • 5 yr local recurrence (LR) rate: 5% (0% to 37%) • Balloon catheter brachytherapy (MammoSite) • LR rate: 0% (F/U11 to 29 months) • Infection rate 16% • 3-D conformal external beam radiotherapy • LR rate: 0 to 25% Arthur, et al., J Clin Oncol 23:1726, 2005.

47. Clinical Trial – NSABP B39 • Partial breast irradiation trial • Tumor size < 3 cm • Unifocal tumor • After lumpectomy, randomized to • External beam radiation (EBRT) • Partial breast irradiation (PBI) • MammoSite • Intracavitary catheters • 3-D conformal EBRT

48. Take Home Message • The role of APBI is evolving • This is NOT the standard of care • Must be considered in the context of • Clinical trial • Careful patient selection • Informed consent

49. Radiotherapy After Mastectomy • Pre-1997: NOT indicated except for • Positive margins • High risk for local failure • Locally advance breast cancer • Inflammatory breast cancer • Post-1997 • Overgaard, et al., NEJM 337:949, 1997. • Danish Breast Cancer Cooperative Group • Ragaz, et al., NEJM 337:956, 1997. • British Columbia • Postmastectomy radiotherapy became relevant

50. Postmastectomy Radiotherapy (PMRT) • ASCO Expert Panel • Reviewed data from 18 randomized clinical trials (RCTs) • Reduction in risk for local failure (LF) • By two thirds to three quarters, proportionally • In practical terms: • Reduction of LF from 8 per 100 patients • To 2-3 per 100 patients Recht, et al., J Clin Oncol19(5):1539, 2001