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Learn about breast cancer staging, prevention, and high-risk patient management. Understand screening recommendations, targeted therapies, and risk assessment tools for early detection. Explore improved survival outcomes and options for treatment.
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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 • 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
Introduction: Breast Cancer Unit 3: Major Cancers, Prevention, & Staging
Breast Cancer StagingAJCC 7th edition Surveillance Epidemiology and End Results Summary statistics 2000
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
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
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
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
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
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
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
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
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
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.
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
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
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
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
Cumulative Incidence of Invasive and Non-invasive Breast Cancer Vogel V et al: JAMA 295(23): 2727-2741, 2006
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
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
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.
LatissimusDorsi Flap TRAM Flap
Breast presentations Presenting SXLikelihood CA Risk missed dx Palpable mass HighLow Abnormal mammo Vague nodularity Nipple discharge Areolar eczema Breast pain Breast infection LowHigh
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
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
Abnormal Mammogram • BIRADS 0 ------> more films • BIRADS 1,2 ----> routine screening • BIRADS 3 ------> 6 mo f/u w/ imaging • BIRADS 4,5,6 -> referral
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
Vague nodularity • May be more common than discrete mass • Understand normal breast tissue densities on physical exam • Role of further imaging studies/biopsy
Benign features induced bilateral color: green, gray, brown Suspicious features spontaneous unilateral color: serosanguinous, bloody, watery Nipple discharge
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
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
Breast Infection • Determine underlying etiology • Understand usual age group distribution • Treat short course of antibiotics • Early vs. late referral for biopsy
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
Trends: Treatment of Breast Cancer • Surgical Oncology • Less is more • Medical Oncology • Targeted therapy • Radiation Oncology • Options for treatment
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…
Biopsy • Percutaneous • U/S guided • Stereotactic • FNA • Open Incisional • Not excising entire lesion • Open excisional • Excising entire lesion, but not wide margins
Surgical Oncology Options • Breast conserving surgery • Lumpectomy/Partial mastectomy • Mastectomy • Modified Radical • Simple/Total • Skin sparing • Reconstruction • Immediate • Delayed
Lymph Nodes • Sentinel Lymph node biopsy • Blue dye • Technetium sulfur colloid • Axillary dissection • Risks: nerve injury and lymphedema
Medical Oncology“Targeted Therapy” • Neoadjuvant approaches • Determination for Chemotherapy • Adjuvant! online • OncotypeDx • Hormonal therapies • Tamoxifen • Arimidex/Femara • Biologic therapy • Herceptin
Neoadjuvant • Chemotherapy or hormone therapy given PRIOR to surgical excision • Benefits: • Can determine effectiveness of therapy • Can shrink tumor for breast conservation
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
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
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
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
Definition of Brachytherapy: “therapy given at arms length” Implantation of radioactive material directly into various malignancies “Radiation from the inside out”