Breast Cancer

1
Breast Cancer

• November 26, 2012

2
Introduction

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

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Gross Anatomy

• Sappys plexus lymphatics under areolar complex
• 75 of lymphatics flow to axilla

4
Microscopic Anatomy

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

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Presentation

• Breast lump
• Abnormal mammogram
• Axillary lympadenopathy
• Metastatic disease

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Familial Breast Cancer

• Cause 5-10 of all cancer and 25 in women lt30
  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,

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Screening Mammography

• Recommendations
• Biannually or annually in 40-49 y/o
• Annually in gt50 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)

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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

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Risk of Future Invasive Breast Carcinoma Based on
Histologic Diagnosis from Breast Biopsies

• No Increase
• AdenosisApocrine metaplasiaCysts, small or
  largeMild hyperplasia (gt2 but lt5 cells
  deep)Duct ectasiaFibroadenomaFibrosisMastitis,
  inflammatoryPeriductal mastitisSquamous
  metaplasia
• Slightly Increased (relative risk, 1.52)
• Moderate or florid hyperplasia, solid or
  papillaryDuct papilloma with fibrovascular
  coreSclerosing adenosis, well-developed
• Moderately Increased (relative risk, 45)
• Atypical hyperplasia, ductal or lobular

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Benign Breast Masses

• Cysts
• Fibroadenoma
• Hamartoma/Adenoma
• Abscess
• Papillomas
• Sclerosing adenosis
• Radial scar
• Fat necrosis

Papilloma
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Maligant Breast Masses

• Ductal carcinoma
• DCIS
• Invasive
• Lobular carcinoma
• LCIS
• Invasive
• Inflammatory carcinoma
• Pagets disease
• Phyllodes tumor
• Angiosarcoma

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Ductal carcinoma
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DCIS

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

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Lobular carcinoma
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Invasive Histology

• Ductal NOS
• Lobular
• Mucinous
• Tubular
• Medullary

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Staging

• Tumor
• Tis in situ
• T1 lt2cm
• T2 2-5cm
• T3 gt5cm
• 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 gt10 nodes or combo of axillary and int mam
  nodes
• mic micoroscopic posivitiy, mol molecular
  posiivity
• Metastasis

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Staging
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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
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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

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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)

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Radiation after mastectomy?

• 2 Danish studies and one Britsh study
• Recommend in gt3 nodes positive,
  aggressive/large tumors or extranodal invasion
• Decreased local or regional recurrence
• /- survival benefit

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Sentinel node biopsy

• Contraindications
• Clinically positive nodes, pregnant or nursing,
  prior axillary surgery, locally advanced disease
• False negative rate 3.1
• Macrometases (gt0.2cm) 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 gt4 nodes
  positive
• NSABP (B-32) in progress

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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

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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)
• lt45mm 0 microinvasion
• 45-55mm 17 microinvasion
• gt55mm 48 microinvasion

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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-

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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

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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

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Chemotherapy

• Early Breast Cancer Trialists Collaborative
  Group
• Decreases recurrence (12) and death (11)
  regardless of nodal status
• Indications
• All patients except node negative, lt10mm 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

29
Other breast cancers

• Inflammatory ca
• Carcinoma invading lymphatic ducts
• Chemotherapy, mastectomy, radiation
• 50 survival at 5 years

30
Other breast cancers

• Pagets disease
• Intraepithelial extesion of ductal ca
• Excision with nipple-areolar complex
• Sentinel node if invasive ca
• Mastectomy

31
Other breast cancers

• Phyllodes tumor
• lt1 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
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Angiosarcoma

• Risk factors
• Radiation
• Lymphedema
• Treatment
• Excision, radiation

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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