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