Breast Cancer

Introduction Most common female cancer Accounts for 32% of all female cancer 211,300 new cases yearly and rising 40,000 deaths yearly

Gross Anatomy Sappy’s plexus – lymphatics under areolar complex 75% of lymphatics flow to axilla

Microscopic Anatomy Stromal tissue Connective tissue, capillaries, lymphocytes, etc. Adipose tissue Ductal tissue Squamous epithelium Columnar or cuboidal epithelium Lobular tissue

Presentation Breast lump Abnormal mammogram Axillary lympadenopathy Metastatic disease

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 BRCA % - breast 20-30% - ovarian Increased risk for prostate, pancreatic, laryngeal,

Screening Mammography Recommendations Biannually or annually in 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%)

Biopsy techniques FNA Diagnostic and therapeutic in cystic lesions Core needle U/S guided or sterotatic 90% effective in establishing diagnosis Atypia – need excision Sterotatic Needle localization Excision biopsy

Risk of Future Invasive Breast Carcinoma Based on Histologic Diagnosis from Breast Biopsies No Increase Adenosis Apocrine metaplasia Cysts, small or large Mild hyperplasia (>2 but <5 cells deep) Duct ectasia Fibroadenoma Fibrosis Mastitis, inflammatory Periductal mastitis Squamous metaplasia Slightly Increased (relative risk, 1.5–2) Moderate or florid hyperplasia, solid or papillary Duct papilloma with fibrovascular core Sclerosing adenosis, well-developed Moderately Increased (relative risk, 4–5) Atypical hyperplasia, ductal or lobular

Benign Breast Masses Cysts Fibroadenoma Hamartoma/Adenoma Abscess Papillomas Sclerosing adenosis Radial scar Fat necrosis Papilloma

Maligant Breast Masses Ductal carcinoma DCIS Invasive Lobular carcinoma LCIS Invasive Inflammatory carcinoma Paget’s disease Phyllodes tumor Angiosarcoma

Ductal carcinoma

DCIS Ductal carcinoma in situ (DCIS)  1. Solid type*  2. Cribiform type  3. Papillary type  4. Comedo type*

Lobular carcinoma

Invasive Histology A.Ductal NOS B.Lobular C.Mucinous D.Tubular E.Medullary

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 int mam node N2: 4-9 axillary nodes or palpalbe int mam node N3: >10 nodes or combo of axillary and int mam nodes {mic micoroscopic posivitiy, mol molecular posiivity Metastasis

Staging

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) Simple mastectomyModified radical

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

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 Mastecomy vs 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)

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

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

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 maligant breast ca for all DCIS

Treatment of DCIS Nodal involvement 3.6% of DCIS pts have positive nodes in mastectomy specimins 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

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-

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

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

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

Other breast cancers Inflammatory ca Carcinoma invading lymphatic ducts Chemotherapy, mastectomy, radiation 50% survival at 5 years

Other breast cancers Paget’s disease Intraepithelial extesion of ductal ca Excision with nipple-areolar complex Sentinel node if invasive ca Mastectomy

Other breast cancers Phyllodes tumor <1% of breast tumors Age Similar in appearance to fibroadenoma 4% recurrence after excision 0.9% axillary spread Radiation, chemotherapy, tamoxifen ?? Phyllodes tumorFibroadenoma

Angiosarcoma Risk factors  Radiation  Lymphedema Treatment  Excision, radiation

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