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  1. 1. Breast Cancer<br />
  2. 2. Introduction<br />Most common female cancer<br />Accounts for 32% of all female cancer<br />211,300 new cases yearly and rising<br />40,000 deaths yearly<br />
  3. 3. Gross Anatomy<br /><ul><li>Sappy’s plexus – lymphatics under areolar complex
  4. 4. 75% of lymphatics flow to axilla</li></li></ul><li>Microscopic Anatomy<br />Stromal tissue<br />Connective tissue, capillaries, lymphocytes, etc.<br />Adipose tissue<br />Ductal tissue<br />Squamous epithelium<br />Columnar or cuboidal <br /> epithelium<br />Lobular tissue<br />
  5. 5. Presentation<br />Breast lump<br />Abnormal mammogram<br />Axillarylympadenopathy<br />Metastatic disease<br />
  6. 6. Familial Breast Cancer<br />Cause 5-10% of all cancer and 25% in women &lt;30 y/o<br />BRCA2<br />Causes 40% of familial breast CA<br />50-70% - breast<br />15-45% - ovarian<br />Increased risk for prostate, colon<br />BRCA1<br />50-70% - breast<br />20-30% - ovarian<br />Increased risk for prostate, pancreatic, laryngeal,<br />
  7. 7. Screening Mammography<br />Recommendations<br />Biannually or annually in 40-49 y/o<br />Annually in &gt;50 y/o<br />15% relative risk reduction<br />Birads<br />0 - Incomplete assessment; need additional imaging evaluation <br />1 - Negative; routine mammogram in 1 year recommended <br />2 - Benign finding; routine mammogram in 1 year recommended <br />3 - Probably benign finding; short-term follow-up suggested (3%)<br />4 - Suspicious abnormality; biopsy should be considered (30%)<br />5 - Highly suggestive of malignancy; appropriate action should be taken (94%)<br />
  8. 8. Biopsy techniques<br />FNA<br />Diagnostic and therapeutic in cystic lesions<br />Core needle<br />U/S guided or sterotatic<br />90% effective in establishing diagnosis<br />Atypia – need excision<br />Stereotatic<br />Needle localization<br />Excision biopsy<br />
  9. 9. Risk of Future Invasive Breast Carcinoma<br />No Increase <br />AdenosisApocrinemetaplasiaCysts, small or largeMild hyperplasia (&gt;2 but &lt;5 cells deep)Duct ectasiaFibroadenomaFibrosisMastitis, inflammatoryPeriductal mastitisSquamousmetaplasia<br />Slightly Increased (relative risk, 1.5–2) <br />Moderate or florid hyperplasia, solid or papillaryDuct papilloma with fibrovascular coreSclerosingadenosis, well-developed<br />Moderately Increased (relative risk, 4–5) <br />Atypical hyperplasia, ductal or lobular<br />
  10. 10. Benign Breast Masses<br />Cysts<br />Fibroadenoma<br />Hamartoma/Adenoma<br />Abscess<br />Papillomas<br />Sclerosing adenosis<br />Radial scar<br />Fat necrosis<br />Papilloma<br />
  11. 11. Maligant Breast Masses<br />Ductal carcinoma<br />DCIS<br />Invasive<br />Lobular carcinoma<br />LCIS<br />Invasive<br />Inflammatory carcinoma<br />Paget’s disease<br />Phyllodes tumor<br />Angiosarcoma<br />
  12. 12. Ductal carcinoma<br />
  13. 13. DCIS<br />Ductal carcinoma in situ (DCIS)<br />1. Solid type*<br />2. Cribiform type<br />3. Papillary type<br />4. Comedo type*<br />
  14. 14. Lobular carcinoma<br />
  15. 15. Invasive Histology<br />Ductal NOS<br />Lobular<br />Mucinous<br />Tubular<br />Medullary<br />
  16. 16. Staging<br />Tumor<br />Tis: in situ<br />T1: &lt;2cm<br />T2: 2-5cm<br />T3: &gt;5cm<br />T4: invasion of skin or chest wall<br />Node<br />N1: 1-3 axillary nodes or intmam node<br />N2: 4-9 axillary nodes or palpable intmam node<br />N3: &gt;10 nodes or combo of axillary and intmam nodes<br />{micmicoroscopicposivitiy, mol molecular posiivity<br />Metastasis<br />
  17. 17. Modified Radical Mastectomy<br />Entire breast tissue and Level I & II nodes<br />Survival at 10 yrs<br />Negative nodes – 82% (5% local recurrence)<br />Positive nodes – 48% (5% local recurrence)<br />Modified radical<br />Simple mastectomy<br />
  18. 18. Breast Treatment Trials<br />NSABP (1971 with B-04 update in 2002)<br />Compared radical, vs modified radical +/- radiation<br />No survival diff for node neg or pos between three arms<br />75% of recurrences occur in 5 years<br />Tumor location not important<br />
  19. 19. Breast Treatment Trials<br />Ontario study<br />All pts got lumpectomy, randomized to radiation or no radiation<br />25% failure rate without radiation, 5% with<br />NSABP B-06<br />Mastecomyvs lumpectomy vs lumpectomy with radiation<br />No difference in survival<br />39% recur with lumpectomy, reduced to 14% with radiation, 3-4% with mastectomy<br />0.5-1% per year recurrence rate for life with BCT and radiation<br />2-5% complication rate with radiation (rib fx, pericarditis, cosmesis)<br />
  20. 20. Radiation after mastectomy?<br />2 Danish studies and one Britsh study<br />Recommend in: &gt;3 nodes positive, aggressive/large tumors or extranodal invasion<br />Decreased local or regional recurrence<br />+/- survival benefit<br />
  21. 21. Sentinel node biopsy<br />Contraindications:<br />Clinically positive nodes, pregnant or nursing, prior axillary surgery, locally advanced disease<br />False negative rate 3.1%<br />Macrometases (&gt;0.2cm) so recommended pathology cuts are 0.2 cm<br />Micrometases (IHC staining) 37% death rate vs 50% of those with macrometases<br />If sentinel node positive 43% will have other nodes positive and 24% will have &gt;4 nodes positive<br />NSABP (B-32) in progress<br />
  22. 22. Treatment of DCIS<br />600% increase after mammography<br />Options<br />Mastectomy – 1% breast ca mortality<br />Large tumors, multicentric, positive margins after reexcision, <br />Lumpectomy and radiation<br />Radiation decreases local recurrence by 50%<br />Of those that recur 50/50 DCIS vs Invasive<br />0-3% chance of dying of malignant breast ca for all DCIS<br />
  23. 23. Treatment of DCIS<br />Nodal involvement<br />3.6% of DCIS pts have positive nodes in mastectomy specimens<br />By definition DCIS has no access to lymphatics<br />Size may matter (111 DCIS tumors evaluated)<br />&lt;45mm – 0% microinvasion<br />45-55mm – 17% microinvasion<br />&gt;55mm – 48% microinvasion<br />
  24. 24. Tamoxifen in DCIS<br />NSABP (B-24)<br />Determine benefit of tamoxifen in lumpectomy plus radiation pts<br />31% decrease in ipsilateral, 47% in contralateral, 31% decrease all together <br />Retrospectively looked at ER status<br />75% of DCIS is ER+<br />59% reduction in ER+ pts<br />No significant reduction in ER-<br />
  25. 25. Treatment for invasive breast ca<br />Locally advanced is likely already metastatic in most<br />Surgery and radiation alone make no difference on survival<br />Chemotherapy & +/- Tamoxifen<br />Neoadjuvant chemotherapy<br />7 randomized trials<br />No survival benefit<br />50-80% response<br />May allow for BCT in large tumors<br />Sentinel node before chemo<br />
  26. 26. Tamoxifen<br />Indications<br />ER + breast ca<br />LCIS<br />BRCA1/2<br />Increased overall risk<br />Benefits<br />Decreases risk of ca in other breast by 47-80% <br />Draw backs<br />Increases endometrial ca risk by 2.5, PE 3.0, DVT 1.7<br />Source: NSABP P-1 trial<br />
  27. 27. Chemotherapy<br />Early Breast Cancer Trialists’ Collaborative Group<br />Decreases recurrence (12%) and death (11%) regardless of nodal status<br />Indications<br />All patients except node negative, &lt;10mm tumors<br />Regimens<br />Multidrug combination chemotherapy<br />Tamoxifen or aromatse inhibitor - ER positive tumors<br />Herceptin (trastuzumab) – HER2/neu positive tumors<br />NSABP B-31 – 33% reduction in risk of death<br />
  28. 28. Other breast cancers<br />Inflammatory ca<br />Carcinoma invading lymphatic ducts<br />Chemotherapy, mastectomy, radiation<br />50% survival at 5 years<br />
  29. 29. Other breast cancers<br />Paget’s disease<br />Intraepithelial extesion of ductal ca<br />Excision with nipple-areolar complex<br />Sentinel node if invasive ca<br />Mastectomy<br />
  30. 30. Other breast cancers<br />Phyllodes tumor<br />&lt;1% of breast tumors<br />Age 30-45<br />Similar in appearance to fibroadenoma<br />4% recurrence after excision<br />0.9% axillary spread<br />Radiation, chemotherapy, tamoxifen ??<br />Phyllodes tumor<br />Fibroadenoma<br />
  31. 31. Angiosarcoma<br />Risk factors<br />Radiation<br />Lymphedema<br />Treatment<br />Excision, radiation<br />
  32. 32. Male breast cancer<br />90% are invasive at time of diagnosis<br />80% ER+, 75% PR+, 30% HER2/neu<br />More invade into pectoralis<br />Treatment same as for female ca<br />