Breast Cancer 3x261t

Breast Cancer

Introduction Most common female cancer  s 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 

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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    

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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,

Screening Mammography 

Recommendations  

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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%)

Biopsy techniques 

FNA 

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Core needle   

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Diagnostic and therapeutic in cystic lesions 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 

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Slightly Increased (relative risk, 1.5–2) 

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Adenosis Apocrine metaplasia Cysts, small or large Mild hyperplasia (>2 but <5 cells deep) Duct ectasia Fibroadenoma Fibrosis Mastitis, inflammatory Periductal mastitis Squamous metaplasia

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  

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Lobular carcinoma  

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DCIS Invasive 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     

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Node    

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Tis: in situ T1: <2cm T2: 2-5cm T3: >5cm T4: invasion of skin or chest wall 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 mastectomy

Modified 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  

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All pts got lumpectomy, randomized to radiation or no radiation 25% failure rate without radiation, 5% with

NSABP B-06   

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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: 

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False negative rate 3.1%   

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Clinically positive nodes, pregnant or nursing, prior axillary surgery, locally advanced disease 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 

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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  

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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

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Sentinel node before chemo

Tamoxifen 

Indications    

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Benefits 

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ER + breast ca LCIS BRCA1/2 Increased overall risk

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 

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Indications 

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Decreases recurrence (12%) and death (11%) regardless of nodal status 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 30-45 Similar in appearance to fibroadenoma 4% recurrence after excision 0.9% axillary spread Radiation, chemotherapy, tamoxifen ??

Phyllodes tumor

Fibroadenoma

Angiosarcoma 

Risk factors  

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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 