Surgical Breast Pathology Juan C. Cendan, MD Assistant Professor of Surgery Objectives of Lecture • Categorize risk factors for cancer – Highlight future cancer risk for a given benign lesion • Describe diagnostic workup for breast masses and tools available to the clinician • Provide up-to-date guidelines in the screening and diagnosis of breast masses • Brief review of surgical options and implications in patients with breast cancer Assessment of Risk/History • Four major risks (increase RR by 4x): – Family history • 1st degree relatives • Age at diagnosis, BRCA1/2 risk – Atypical hyperplasia on prior biopsies – Personal breast cancer history – LCIS Assessment of Risk/History • Four Minor Risk Factors: 1-2x RR – – – – – Early menarche Long interval from menarche to 1st child Nulliparity Ovarian or endometrial cancer Estrogen therapy after menopause Physical Exam • Be systematic – Inspection of breasts: sitting up, then recumbent • “Strip method” – Nipples – Lymph nodes Clinical Examination of a Patient with Benign Breast Disease Santen, R. J. et al. N Engl J Med 2005;353:275-285 Common Benign Breast Disorders in Women Santen, R. J. et al. N Engl J Med 2005;353:275-285 Diagnostics • Standard screening mammogram – CC and MLO • Diagnostic mammogram – Above, plus compression/additional views • In either case, 5-10% false negative and 90-95% sensitivity Cranio-caudal (CC) view and mediolateral oblique (MLO) mammographic view Atypical Hyperplasia Histopathological Appearance of Benign Breast Disease (Hematoxylin and Eosin) Panel A shows nonproliferative fibrocystic changes:the architecture of the terminal-duct lobular unit is distorted by the formation of microcysts,associated with interlobular fibrosis.Panel B shows proliferative hyperplasia without atypia. This is adenosis,a distinctive form of hyperplasia characterized by the proliferation of lobular acini,forming crowded gland-like structures.For comparison,a normal lobule is on the left side.Panel C also shows proliferative hyperplasia without atypia.This is moderate ductal hyperplasia,which is characterized by a duct that is partially distended by hyperplastic epithelium within the lumen.Panel D again shows proliferative hyperplasia without atypia,but this is florid ductal hyperplasia:the involved duct is greatly expanded by a crowded,jumbled-appearing epithelial proliferation.Panel E shows atypical ductal hyperplasia:these proliferations are characterized by a combination of architectural complexity with partially formed secondary lumens and mild nuclear hyperchromasia in the epithelial-cell population.Panel F shows atypical lobular hyperplasia:monotonous cells fill the lumens of partially distended acini in this terminal-duct lobular unit. Hartmann, L. C. et al. N Engl J Med 2005;353:229-237 Diagnostics • Ultrasound – Useful in the young – Useful in pregnant women – Delineates solid vs cystic • MRI – Possibly the future of breast diagnostics, not there yet, limitations with biopsy Solid (Suspicious) Breast Mass Cyst Fibroadenoma Biopsy techniques • Palpable solid mass – Needle or core biopsy – Incisional or excisional biopsy • Non-palpable mass – Stereotactic core – Stereotactic “mammotome” – Needle localized biopsy Some Benign Conditions • Nipple Discharge – Incidence of malignancy when bloody (1015%) and unilateral, though usually papilloma – More likely cystic or duct ectasia – Consider prolactin if bilateral Benign, con’t • Fibroadenoma – – – – Very common in young women Freely mobile and smooth Characteristic u/s appearance Half of adenomas resolve if <3cm over 5yrs • Large adenomas should be biopsied to exclude rare phylloides tumor Benign, con’t • Cysts – Due to relative excess estrogen, usually in 4-5th decades – Fluctuate with menses – Aspirate, if bloody then excise, send fluid for path the first time Benign, con’t • Abscess, – – – – Usually in lactating women Painful and erythematous Usually staph and strep Drainage and antibiotics indicated • Rarely, can aspirate and treat with antibiotics • Caveats, in nonlactating (Ca), non-resolving (atypical infection), inflammatory cancer Classification of Benign Breast Lesions on Histologic Examination, According to the Relative Risk of Breast Cancer Santen, R. J. et al. N Engl J Med 2005;353:275-285 Risk of Breast Cancer According to Breast Density in Premenopausal and Postmenopausal Women Santen, R. J. et al. N Engl J Med 2005;353:275-285 Risk of cancer of benign breast lesions, Hartmann et al, NEJM 2005 Lesion RR Non 1.27 Proliferative FHx Age Weak Strong <45 >55 0.9 1.62 1.27 1.31 Proliferative no atypia 1.88 1.57 2.2 2.27 1.63 Atypia 4.24 2.95 4.0 7 3.37 Gail, J Natl Cancer Inst. 1989 Dec 20;81(24):1879-86. Race W W W W W Age 45 62 62 62 62 Age 1st menses 13 13 13 13 13 Age 1st live birth 21 21 21 21 21 #1a relatives 0 0 1 1 1 # prior breast bx 0 0 0 3 3 ?Atypia N N N N Y % Risk per year .7 1.4 2.9 4.4 8.4 Risk over life 8.6 6.2 12.8 18.6 32.6 Examples of Outcomes among 100 Women Followed for an Average of 15 Years: Explaining Relative Risk Calculations to Patients… Start with known risk and “translate” it to an absolute risk Elmore, J. G. et al. N Engl J Med 2005;353:297-299 Cancer • Most women with breast cancer have no risk factors! • Role of dietary fat, estrogen • Breast cancer genes responsible for 35% only Cancer • DCIS – Carcinoma in situ – Usually found on mammography as microcalcifications – Felt to progress to invasive in 30-50% if untreated – Subtypes: comedo highest risk Cancer • DCIS, con’t – Treatment • Non-invasive, so risk of LN disease is minimal • Must treat the breast, options: – Excise with large enough margins (>1cm) in a small tumor – Or, Excise and radiate – Or, Mastectomy +/- reconstruction Cancer • Invasive Ductal Cancer – “Garden variety breast cancer” – More often presents with mass than DCIS – Treatment: • BREAST: Excise and RT or mastectomy, Cannot just excise with margins (30-40% recur) • Lymph Nodes: Must be sampled for staging – Sentinel Node vs Axillary Dissection Cancer • Chemotherapy – Recommended for tumors >1cm in most patients – Recommended if lymph nodes are positive – 8 recommended chemo protocols at this time!! • ER positivity and Tamoxifen Cancer • Survival Stage I II III IV Survival Rate % 96% 82% 53% 18%
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