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Module 1: Breast Cancer

Module 1: Breast Cancer. Instructor Sheryl G. A. Gabram MD MBA FACS Professor of Surgery, Emory University Director Avon Comprehensive Breast Center at Grady. Unit 3: Major Cancers, Prevention, & Staging. Objectives. To discuss breast screening recommendations

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Module 1: Breast Cancer

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  1. Module 1: Breast Cancer Instructor Sheryl G. A. Gabram MD MBA FACS Professor of Surgery, Emory University Director Avon Comprehensive Breast Center at Grady Unit 3: Major Cancers, Prevention, & Staging

  2. Objectives • To discuss breast screening recommendations • To identify and provide recommendations for high risk and symptomatic breast patients • To learn about current Surgical Care Less is More • To become familiar with Medical Oncology Targeted Therapy • To understand the role of Radiation Oncology Options for Treatment Unit 3: Major Cancers, Prevention, & Staging

  3. Introduction: Breast Cancer Unit 3: Major Cancers, Prevention, & Staging

  4. Breast Cancer StagingAJCC 7th edition Surveillance Epidemiology and End Results Summary statistics 2000

  5. Improvement in survival…

  6. Improvement in survival due to…. • Earlier detection • Identification and referral for breast symptoms • Increased use of screening mammography • Intense surveillance of high risk patients • Targeted therapy • Hormonal, chemotherapeutic, biologic therapy Allows for less surgery and possibly less radiotherapy—impact on morbidity

  7. ACS recommendations for Early Breast Cancer Detection • No baseline mammography • Starting screening annually at age 40 as long as in good health • CBE start in 20s-30s every 3 years, asymptomatic preferably annually >40 (prior to mammography) • Beginning in 20s ♀ should be told +/- of BSE, report breast changes promptly to MD • Women at ↑risk should talk to MD about more frequent exams/novel imaging at younger age

  8. Reproductive: age at menarche, parity, age at 1st full-term pregnancy, age at menopause Endogenous hormonelevels: estradiol, androgens, prolactin, insulin, ?melatonin Exogenous hormoneexposure: HRT Mammographic breast density Atypical hyperplasia & lobular carcinoma in situ Diet: caloric intake, fat intake Physical activity Body habitus: height, weight, BMI, post-menopausal weight gain Alcohol intake Prior chest wall irradiation Family historyof breast or ovarian cancer Established Breast Cancer Risk Factors

  9. Modified Gail Risk: Questions • Age • Age of menses • Age of first live birth • Number of 1st degree relatives breast cancer • Breast biopsy and if yes, ADH? • Ethnicity Gail MH et al: J Natl Cancer Inst 81:1879, 1989

  10. Breast Cancer Risk Continuum Reproductive risk factors Atypical hyperplasia Familial clustering BRCA1 & BRCA2 carriers Non-BRCA hereditary syndromes No risk factors 5% 10% 20% 30% 40% 50% 60% 70% 80% Lifetime Breast Cancer Risk

  11. Risk Analysis: Modified Gail Model Modified Gail Model 5 year risk: 2.6% Lifetime risk: 29.3% Age: 39 Age at menarche: 12 Previous breast biopsies: 2 Atypical hyperplasia: No Age at birth of 1st child: none Sister with breast cancer: 1 Ethnicity: Caucasian

  12. Estimating Breast Cancer Risk Age: 39 Age at menarche: 12 Previous breast biopsies: 0 Atypical hyperplasia: No Age at birth of 1st child: none Mother/sisters with breast cancer: 1 Beth Ovarian, 57 BRCA1 carrier Gail model Diana Breast, 32 5 yr: 1% 80% Life: 18.9% Cindy 39, unaffected

  13. Pedigree Assessment Tool • Cindy 39 yo Caucasian female unaffected • Family history: • Mother with ovarian cancer • Sister age 32 with breast cancer Maternal 4 5 9 Paternal 4 0 4 Hoskins, et al. Cancer 2006;107:1769-76

  14. New Standards of Care for Women at Increased Breast Cancer Risk • Intensified Surveillance (screening breast MRI) • American Cancer Society (2007) • CA Cancer Journal for Clinicians, March/April 2007 • Chemoprevention: SERM’s USPSTF (2002) Annals of Internal Medicine, July 2002 • Genetic counseling and predictive testing of BRCA genesUSPSTF (2005) • Annals of Internal Medicine, September 2005

  15. Spectrum of Care Options Enhanced screening Chemoprevention Prophylactic Surgery Life style changes (Encourage referral for genetic counseling/testing) Gabram SGA et al: Breast Cancer and Res Treatment 2004;88: S95.

  16. Breast Magnetic Resonance Imaging

  17. ACS Guidelines for Breast Screening with MRI as an Adjunct to Mammography • Recommend (Based on Evidence) • BRCA1 or BRCA2 mutation • 1st degree relative BRCA carrier, untested • Lifetime risk 20-25% • Recommend (Based on Expert Consensus) • Radiation to chest between ages 10 and 30 • Li-Fraumeni and 1st degree • Cowden’s and 1st degree Saslow D, et al: CA Cancer J Clin 57:75-89, 2007

  18. ACS Guidelines for Breast Screening with MRI as an Adjunct to Mammography • Insufficient Evidence for or against • Lifetime risk 15-20% • LCIS, ADH, ALH • Hetero or extremely dense breasts • Personal history of breast cancer • Recommend Against (Expert Consensus) • Women at <15% lifetime risk Saslow D, et al: CA Cancer J Clin 57:75-89, 2007

  19. BREAST CANCER CHEMOPREVENTION Stop Progression Reverse Reverse Normal Breast Intraepithelial Neoplasia Invasive Cancer Terminal Lobule Duct Unit Simple Hyper- plasia Low Grade Atypical Hyper- plasia High Grade Atypical Hyper- plasia Low Grade In Situ High Grade In Situ Invasive Cancer

  20. Tamoxifen Reduced Invasive Breast Cancer in All Ages Placebo Tamoxifen 154 85 # Invasive Breast Cancers 59 46 49 38 24 23 Total 35-49 50-59 60 + Age Group

  21. Cumulative Incidence of Invasive and Non-invasive Breast Cancer Vogel V et al: JAMA 295(23): 2727-2741, 2006

  22. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer • Mayo clinic retrospective review 1960-1993 • 639 women (425 mod risk, 214 high risk) • Risk reduction (Moderate/High) • 37.4 expected, 4 cancers(89.5% decrease) • 38.7% vs 1.4% (90% decrease) • PM decreases incidence of breast cancer in mod/high risk pts Hartmann LC et al: NEJM 340: 77, 1999

  23. Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation • Prospective study for BRCA1/2 pts, 24.2 months • Chose: surveillance or risk-reducing surgery • Results (n=72 and n=98 respectively) • Surveillance: 8 Br CA, 4 ovar CA, 1 peritoneal CA • Surgery: 3 Br CA, 1 peritoneal CA • BRCA1/2 pts, risk reducing salpingo-oophorectomy decreases Breast (by 50%) and GYN cancers Kauff ND et al: NEJM 346: 1609-1615, 2002

  24. Prophylactic Surgery Should not be performed on healthy women before offering genetic counseling/testing Women tend to overestimate their risk Never an emergent or urgent procedure Body image and effect on sexuality Wood WC: Oncology 18: 28-32, 2004.

  25. Implants/Expanders

  26. LatissimusDorsi Flap TRAM Flap

  27. Breast presentations Presenting SXLikelihood CA Risk missed dx Palpable mass HighLow Abnormal mammo Vague nodularity Nipple discharge Areolar eczema Breast pain Breast infection LowHigh

  28. Identifying a Mass • Distinct from surrounding tissues • Generally asymmetrical • Remember normal structures: • Rib, costochondral junction • firm margin at edge of breast • edge of defect due to excisional biopsy Donegan WL: NEJM 327: 937-942, 1992

  29. Diagnostic vs Screening • Screening: • Consists of four views—two views of each breast. • For women without any specific breast complaints • Diagnostic: • The four standard views are supplemented with additional views, and ultrasound or MRI as needed. • For women who are having symptoms such as a lump or unusual nipple discharge or pain. • Generally read by the radiologist right after it has been performed • For all male patients with symptoms and for those with implants

  30. Abnormal Mammogram • BIRADS 0 ------> more films • BIRADS 1,2 ----> routine screening • BIRADS 3 ------> 6 mo f/u w/ imaging • BIRADS 4,5,6 -> referral

  31. When to screen < 40 yearsMammography • BRCA 1/2 mutation • Strong FH of pre-menopausal breast cancer • Personal history of breast cancer • Diagnosis of ADH or LCIS on biopsy • Hodgkin’s Disease (8 years after XRT) • Preoperative for reduction mammoplasty • Cancer phobia

  32. Vague nodularity • May be more common than discrete mass • Understand normal breast tissue densities on physical exam • Role of further imaging studies/biopsy

  33. Benign features induced bilateral color: green, gray, brown Suspicious features spontaneous unilateral color: serosanguinous, bloody, watery Nipple discharge

  34. Areolar eczema • Rule out Paget’s disease • Punch biopsy • Features of Paget’s • 60% have palpable masses • 66% intraductal, 33% invasive carcinoma • Paget’s cells: large, rounded ovoid intraepidermoid cells with abundant pale cytoplasm

  35. Breast Pain(Mastodynia) • Determine characteristics • non-cyclical, point tenderness, increasing symptoms • Role of imaging modalities • Treatment • reassurance, NSAIDS, withhold caffeine, vitamin E, primrose oil, rarely Danazol

  36. Breast Infection • Determine underlying etiology • Understand usual age group distribution • Treat short course of antibiotics • Early vs. late referral for biopsy

  37. Appropriate referral guidelines • Breast mass: not a simple cyst • Abnormal mammogram: BI-RADS 3/4/5 • Vague nodularity: patient concerned • Nipple discharge: unilateral, spontaneous • Areolar eczema: needs punch biopsy • Focal constant breast pain and MD concerned • Breast infection: persists after Antibiotics

  38. Trends: Treatment of Breast Cancer • Surgical Oncology • Less is more • Medical Oncology • Targeted therapy • Radiation Oncology • Options for treatment

  39. Diagnosis at Surgery Mastectomy 14 day hospital stay Hormonal therapy +/- Chemo therapy +/- Radiation therapy Delayed Reconstruction Core or FNA biopsy Multi-disciplinary Ambulatory/observation Breast Conservation Sentinel node surgery Chemo/Hormonal (pre-op) Radiation options Reconstruction: Immediate vs. delayed Surgical Trend: Less is More That was then… This is Now…

  40. Biopsy • Percutaneous • U/S guided • Stereotactic • FNA • Open Incisional • Not excising entire lesion • Open excisional • Excising entire lesion, but not wide margins

  41. Surgical Oncology Options • Breast conserving surgery • Lumpectomy/Partial mastectomy • Mastectomy • Modified Radical • Simple/Total • Skin sparing • Reconstruction • Immediate • Delayed

  42. Lymph Nodes • Sentinel Lymph node biopsy • Blue dye • Technetium sulfur colloid • Axillary dissection • Risks: nerve injury and lymphedema

  43. Breast Surgical Procedures

  44. Medical Oncology“Targeted Therapy” • Neoadjuvant approaches • Determination for Chemotherapy • Adjuvant! online • OncotypeDx • Hormonal therapies • Tamoxifen • Arimidex/Femara • Biologic therapy • Herceptin

  45. Neoadjuvant • Chemotherapy or hormone therapy given PRIOR to surgical excision • Benefits: • Can determine effectiveness of therapy • Can shrink tumor for breast conservation

  46. My RS is 30, What is the chance of recurrence within 10 yrs? 95% CI Trial Assigning Individualized Options for Treatment: TAILORx Paik et al, NEJM 2004

  47. Radiation Oncology“Options for Treatment” • Indications • Breast conservation • Post mastectomy • Approaches • Standard: CT planning • Intensity modulated radiotherapy (IMRT) • Partial breast irradiation (Mammosite) • 3D conformal radiation therapy • Intra-operative radiation therapy (IORT) Kuerer HM: Ann Surg 239: 338, 2004

  48. Whole Breast Radiation • Goal is to kill microscopic disease that may remain in the breast • Entire breast is targeted with BOOST to tumor bed • 5-6 weeks of daily therapy

  49. NSABP B-06 • Randomized trial to compare segmental mastectomy and with and without radiation and total mastectomy • 5 year results: • Overall survival was no worse with breast conservation therapy • In lumpectomy group, local recurrence rates were lower when radiation was given (8% vs 28%) - Fisher et al NEJM 1985 • 20 year results: • No difference in overall survival • In lumpectomy group, local recurrence rates were lower when radiation was given (39% vs 14%) - Fisher et al NEJM 2003

  50. Definition of Brachytherapy: “therapy given at arms length” Implantation of radioactive material directly into various malignancies “Radiation from the inside out”

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