Breast Cancer Risk Factors and Breast Cancer Early Detection

Breast Cancer Risk Factors and Breast Cancer Early Detection Lisa A. Newman, M.D., M.P.H., F.A.C.S. Professor of Surgery Director, Breast Care Center University of Michigan Ann Arbor, MI

REDUCTION OF THE BREAST CANCER BURDEN Preventing Breast Cancer Reducing breast cancer risk factors Chemoprevention Prophylactic mastectomy Reducing Breast Cancer Mortality Early detection (screening) Improving treatment

Relevance of Topic Importance of understanding breast cancer risk factors Some risk factors are modifiable High-risk women (women most likely to develop breast cancer) might consider alternative screening programs or risk-reducing strategies Importance of breast cancer early detection Breast cancer includes a complex spectrum of disease subtypes Treatment is more likely to be successful for ANY subtype, even the most aggressive

BREAST CANCER RISK FACTORS Clinical Features Menstrual/Reproductive factors Early menarche Late menopause Nulliparity/elderly primigravida (Note: prolonged lactation is PROTECTIVE!) Postmenopausal obesity Prolonged exogenous hormone exposure Hormone Replacement Therapy Heavy alcohol intake

BREAST CANCER RISK FACTORS Clinical Features Family history maternal or paternal lines 1 members and early onset strongest, but extended FH important for comprehensive assessment ethnicity in combination with FH may better assess risk of hereditary cancer Personal history of breast cancer Chest wall irradiation (especially during adolescence and early adult life)

Hereditary Breast Cancer Approximately 180,000 breast cancers diagnosed in the United States annually 6-10% with hereditary etiology majority related to mutations in BRCA 1 or BRCA 2 genes 56-85% of women with BRCA mutations will develop breast cancer by age 70 Increased frequency of mutations with unclear significance in African American Hereditary breast cancer in Africa????

BREAST CANCER RISK FACTORS Clinical Features Family history Menstrual history Histopathologic Features Biopsy evidence of abnormal proliferation

BREAST CANCER RISK FACTORS Histopathologic Features Atypical ductal hyperplasia Atypical lobular hyperplasia Radial Scar Papilloma Lobular carcinoma in situ Note: when these pathologies are identified in a needle biopsy, a surgical biopsy must then be performed for further evaluation

BREAST CANCER RISK FACTORS Approximately 75-80% of breast cancers occur in women with no identifiable risk factors!

SCREENING FOR BREAST CANCER Breast Self-Examination Clinical Breast Examination Screening Mammography Other (Selected Cases) Whole Breast ultrasound MRI Screening guidelines are intended for women with a normal breast exam; any change in breast exam requires a diagnostic evaluation!

SCREENING FOR BREAST CANCER Breast Self-Examination Background Limited data on efficacy, but rational approach for improving breast health awareness Monthly, age 20 years and over approximately 1 week after menstrual period in premenopausal women Technique Visual inspection Upright palpation Supine palpation Breast, axillary, and supraclavicular palpation

SCREENING FOR BREAST CANCER Clinical Breast Examination Background Limited data on effectiveness To be performed by trained health care provider Yearly, after age 20 Alternatively, whenever woman undergoes GYN examination and/or mammogram Technique Visual inspection Upright palpation Supine palpation Breast, axillary, and supraclavicular palpation

PALPABLE BREAST ABNORMALITIES Fibroadenoma Simple Cyst Complex Cyst Fibrocystic, Fibrofatty Nodularities Infectious Abscess Mastitis Neoplasm/Cancer Biopsy necessary to definitively discriminate the benign lumps from the cancers

Danger Signs / Symptoms of Breast Cancer Dominant or discrete lump Bloody nipple discharge Breast skin erythema, puckering, edema Sometimes difficult to distinguish from mastitis Cancer MUST be ruled out promptly if skin changes persist or do not resolve completely with trial of antibiotics Axillary and/or supraclavicular adenopathy Upper extremity lymphedema/secondary to adenopathy

Paget s Disease of the Breast

INDUCTION CHEMOTHERAPY FOR BREAST CANCER PRE-CTX POST-CTX

SCREENING FOR BREAST CANCER Mammography Mammography clinical trials: healthy women randomized to receive regular mammograms versus usual medical care Annually for women age 40 and older optimal results with dedicated breast imaging staff and availability of prior studies for comparison 20-30% lower mortality in screened women because of early detection

Study SCREENING FOR BREAST CANCER Mammography: Why all the controversy? Age at Entry Accrual Interval F/U (yrs) Mamm Interval Mam Views Mortality 40-49 yo HIP 40-49 1963-66 18 12 2 22 Kopperberg 40-49 1977-89 15 24 1 22 Ostergotland 40-49 1978-89 14 24 1 8 Malmo 45-49 1977-90 13 18-24 1,2 28 Edinburgh 45-49 1978-85 13 24 1,2 18 Gothenberg 39-49 1982-84 12 18 1,2 29 Stockholm 40-49 1981-86 11 28 1 5 Canada NBSS 40-49 1980-85 11 12 2 0

MAMMOGRAPHY

Mammography

Mammographic Microcalcifications

Simple vs. Complex Cyst Clinical approach to potentially cystic breast lump when ultrasound imaging is not available: 1. Needle aspiration 2. Proceed to surgical excision if: Aspirate is bloody Mass does not completely resolve Lump/mass recurs

Ultrasound Image of Breast Cancer

Mammogram & Breast Ultrasound: Cancer

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BREAST CANCER RISK FACTORS Approximately 75-80% of breast cancers occur in women with no identifiable risk factors!

SCREENING FOR BREAST CANCER Breast Self-Examination Clinical Breast Examination Screening Mammography Other (Selected Cases) Breast ultrasound MRI Screening guidelines are intended for women with a normal breast exam; any change in breast exam requires a diagnostic evaluation!

SCREENING FOR BREAST CANCER Breast Self-Examination Background Limited data on efficacy, but rational approach for improving breast health awareness Monthly, age 20 years and over approximately 1 week after menstrual period in premenopausal women Technique Visual inspection Upright palpation Supine palpation Breast, axillary, and supraclavicular palpation

MAMMOGRAPHY

SCREENING FOR BREAST CANCER Mammography Annually for women age 40 and older optimal results with dedicated breast imaging staff and availability of prior studies for comparison 30% lower mortality in screened women >49 yrs Controversies: Survival benefits, particularly in women 40-49 yrs Digital versus conventional mammography? Frequency of mammography in highest-risk pts

TYPES OF BREAST ABNORMALITIES Palpable Masses Nonpalpable Masses Image-detected Nipple Discharge Isolated Axillary Adenopathy Breast Pain

DIAGNOSTIC INTERVENTION FOR BREAST ABNORMALITIES Clinical judgment essential Breast cancer screening in frail/elderly women should be guided by medical fitness of patient Selection of intervention may be influenced by patient age, family history Selection of intervention should be guided by level of suspicion regarding nature of abnormality Bx is definitive, but observation and short-interval reevaluation is safe for selected lesions

PALPABLE BREAST ABNORMALITIES Fibroadenoma Simple Cyst Complex Cyst Fibrocystic, Fibrofatty Nodularities Infectious Abscess Mastitis Neoplasm/Cancer

BREAST IMAGING FOR PALPABLE MASSES Mammogram Well-defined versus spiculated lesions Calcifications Multicentricity Contralateral disease? Breast Ultrasound Cystic versus solid nature of lesion Echogenicity and configuration Best performed as a focused study in conjunction with mammographic and clinical correlation

HISTOPATHOLOGIC WORK-UP OF PALPABLE MASSES Open, excisional biopsy (gold standard) Percutaneous, free-hand needle biopsy Fine-needle aspirate (FNA) Core, Tru-Cut needle biopsy Image-directed needle biopsy Ultrasound-guided Stereotactic/mammo-guided Limitations of FNA False negative rate with FNA 15-20% FNA during pregnancy may be difficult to interpret

NON-PALPABLE BREAST ABNORMALITIES Masses Asymmetric densities Calcifications

HISTOPATHOLOGIC WORK-UP OF NON-PALPABLE MASSES Open, excisional biopsy with preop mammo/sonoguided needle/wire localization gold standard specimen mammogram essential Image-directed needle biopsy Ultrasound-guided, or Stereotactic/mammo-guided Core needles generally preferred over FNA Accurate, avoids unnecessary surgery Certain high-risk lesions must be followed by surgery facilitates single-stage cancer-directed surgery planning improved likelihood of margin-negative lumpectomy

Nipple Discharge Physiologic: May be greenish; clear; gold; milky Frequently from multiple ducts Usually secondary to fibrocystic changes and/or hormonal issues Pathologic: Bloody?unilateral, single duct non-bloody May be caused by intraductal papillomas, duct ectasia, or cancer

Bloody Nipple Discharge: Workup Mammogram Subareolar ultrasound Ductogram Goal: to identify a target for biopsy If no focal lesions identified, pt referred for terminal duct excision

Breast Ductogram

Total/Terminal Duct Excision Chassin s Operative Strategy in General Surgery, 3rd ed. 2002

Management of Young Women with Breast Abnormalities Age <30; no focal findings; diffuse pain and/or fibronodularity Observation reasonable Reevaluate patient one week after menstrual cycle Age<30; focal site of dominant nodularity Imaging with ultrasound, mammogram Age 30; any breast complaint Imaging with ultrasound and consideration of mammogram reasonable Referral to BCC in questionable cases Concerns re: lobular CA

SURGERY FOR BREAST CANCER: Evolution Radical Mastectomy Extended Radical Mastectomy Modified Radical Mastectomy Breast Conservation Therapy Breast Reconstruction Delayed Immediate Lymphatic Mapping/Sentinel Lymph Node Biopsy Preoperative chemotherapy

MANAGEMENT OF BREAST CANCER Three Principles Eradicate the primary focus of disease The entire breast must be treated risk of microscopic multicentric foci of disease The axillary nodal basin must be staged

MANAGEMENT OF BREAST CANCER: Standard of Care Modified Radical Mastectomy Removal of breast with axillary surgery Breast Conservation Therapy Lumpectomy, axillary surgery, and breast XRT Systemic therapy (chemotherapy and/or hormonal therapy), depending on tumor stage & features Breast cancer treatment trials: women randomized to lumpectomy vs mastectomy women randomized to surgery + CTX vs surgery alone

Clinical Trials of Mastectomy vs. Breast Conservation Therapy Trial # Pts Max tumor Overall Survival Local Recurrence size Mast BCT Mast BCT Milan Cancer Institute 701 2 cm 76% 79% 6% 5% EORTC 868 5 cm 66% 65% 12% 20% U.S. NCI 237 5 cm 79% 78% 8% 13% NSABP B-06 1855 4 cm 71% 71% 8% Lumpectomy + XRT: 10% Lumpectomy only: 39%

MASTECTOMY VS. BREAST CONSERVATION THERAPY Breast cancer outcome is dependent on disease stage and primary tumor biology Survival equivalence for mastectomy and lumpectomy patients Factors for optimal lumpectomy results Patient wish for breast preservation Access to XRT facility Acceptable tumor/breast size ratio Lumpectomy margins negative for cancer Mammogram free of diffuse calcifications Unicentric disease (one tumor)

BREAST CONSERVATION THERAPY

BREAST RECONSTRUCTION Immediate versus Delayed Autogenous tissue TRAM flap (abdominal skin and fatty tissue) Latissimus dorsi flap (using back tissues) Implant Staged procedure, starting with tissue expander that is subsequently exchanged for the implant Adverse factors Chest wall irradiation Smoking

DELAYED RECONSTRUCTION

BREAST RECONSTRUCTION: Conventional Mastectomy

Skin-Sparing Mastectomy Improves cosmesis with immediate breast reconstruction Resection of nipple-areolar complex, any tumor biopsy scar, and axillary surgery Preservation of uninvolved breast skin Preservation of inframammary fold

SKIN SPARING MASTECTOMY

SKIN-SPARING MASTECTOMY

SKIN SPARING MASTECTOMY

AXILLARY LYMPH NODES AND BREAST CANCER One of the first routes of breast cancer spread Cancer involvement of axillary lymph nodes reflects likelihood of microscopic cancer elsewhere in the body Micrometastases Even patients with early stage breast cancer are at risk for having micrometastases There is no replacement for removal of nodes and microscopic evaluation to look for cancer present within the nodes

Breast Lymphatics

Surgical Staging of the Axilla Axillary Lymph Node Dissection: The Gold standard Morbidity: Lymphedema, Numbness, Shoulder dysfunction Lymphatic Mapping & SLN Bx Most promising technology available for minimizing risks of axillary lymph node surgery without compromising treatment

LYMPHATIC MAPPING AND SENTINEL LYMPH NODE BIOPSY The sentinel lymph nodes are the primary lymph nodes responsible for draining the segment of the breast where the cancer was diagnosed There are two methods of identifying the sentinel lymph nodes Radioisotope injection Blue dye injection Accuracy depends on expertise of surgeon!

Lymphatic Mapping

LYMPHOSCINTIGRAPHY

SENTINEL LYMPH NODE BIOPSY

SYSTEMIC THERAPY FOR BREAST CANCER 15-20% relapse rate for Stage I disease Adjuvant systemic therapy can decrease odds of relapse by 30% consider adjuvant systemic therapy for micrometastases if tumor >1cm, or node-positive Selection of appropriate systemic therapy is essential for improved survival

SYSTEMIC THERAPY FOR Endocrine therapy Tamoxifen Aromatase Inhibitors Chemotherapy Targeted therapy Herceptin BREAST CANCER Selection of appropriate systemic therapy is essential for improved survival

PREOPERATIVE CHEMOTHERAPY Improved chemotherapy for breast cancer results in easier surgery & earlier treatment of micrometastases Allows for monitoring of chemotherapy effectiveness Benefits depend on increased use of needle biopsies Pre-CTX Post-CTX

Common Questions and Concerns Does breast pain indicate that I have cancer? Does breast pain indicate that I don t cancer? Should I get mammograms more frequently if I have a family history of breast cancer? Does exposure to air make a tumor spread? Does stress cause cancer? Can I avoid breast cancer by following a special diet? Can I develop breast cancer by following a special diet? Do brassieres cause breast cancer? Is there any way to prevent breast cancer?