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

BRCA1 50-70% - breast 20-30% - ovarian Increased risk for prostate, pancreatic, laryngeal,

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%)

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

AdenosisApocrine metaplasiaCysts, small or largeMild hyperplasia (>2 but <5 cells deep)Duct ectasiaFibroadenomaFibrosisMastitis, inflammatoryPeriductal mastitisSquamous metaplasia

Slightly Increased (relative risk, 1.5–2) Moderate or florid hyperplasia, solid or papillary

Duct papilloma with fibrovascular coreSclerosing 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 NOSB. LobularC.MucinousD.TubularE. 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 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 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 30-45 Similar in appearance to fibroadenoma 4% recurrence after excision 0.9% axillary spread Radiation, chemotherapy, tamoxifen ??

Phyllodes tumor Fibroadenoma

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