Epidemiology

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Etiology

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Benign cancer

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Intraductal papilloma

• BIoody nipple discharge in pre-menopausal women (vs. Papillary Carcinoma)
• FibrovascuIar projections lined by luminal myoepithelial cells (vs. Papillary Carcinoma)

Mnemonic

• Intraductal = Myoepithelium Included
• Papillary = Myoepithelium Popped

Fibroadenoma

• Refers to a marble-like, rubbery mobile, stromal/glandular benign tumor
• Estrogen sensitive (will enlarge during pregnancy/menstrual cycle)
• Typically occurs in 15-35 y/o women
• Biopsy: fibrous and glandular tissue

Mnemonic

fibROadenoma = estROgen sensitive

Phyllodes tumor

• Refers to a fibroepithelial tumor that ranges from benign (mostly) to malignant (rarely)
• Characteristic leaf-like projections into epithelium-lined stroma & dilated lumen
• Typically occurs in 40-50 y/o women

Malignant cancer

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Noninvasive carcinomas

Ductal carcinoma in situ (DCIS)

• Characteristics
  • No penetration of the basement membrane
  • Preceded by ductal atypia
  • Frequently appears as a pattern of grouped microcalcifications on mammography
  • Higher risk of subsequent ipsilateral invasive carcinoma
• Comedocarcinoma
  • Characteristics: subtype of DCIS characterized by central necrosis

Tip

Noninvasive carcinomas are characterized by the absence of stromal invasion.

Lobular carcinoma in situ (LCIS)

• Refers to proliferation of lobular cells but has not yet invaded basement membrane
• Lacks E-Cadherin

Mnemonic

Lobular Carcinoma Lacks Cadherin

Invasive carcinomas

Invasive ductal carcinoma (IDC)

• Characteristics
  • Most common type of invasive breast cancer (∼ 80%)
  • Aggressive formation of metastases
• Localization
  • Unilateral
  • Mostly unifocal

Medullary breast cancer

• Characteristics
  • Rare subtype of invasive ductal carcinoma
  • Most common tumor associated with the BRCA1 mutation
  • Well-circumscribed soft tumor with smooth borders (may appear benign)
  • Usually triple-negative
  • Lymphadenopathy
• Differential diagnosis: fibroadenoma

Invasive lobular carcinoma (ILC)

• Characteristics
  • ∼ 10% of all invasive breast carcinomas
  • Less aggressive than ductal carcinoma
  • Monomorphic cells in a single file pattern due to a decrease in E-cadherin expression
• Localization
  • Bilateral in ∼ 20% of cases
  • Frequently multifocal

Mnemonic

ILC = Individual Line Carcinoma

Clinical features

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Locally advanced disease

• Skin
  • Retractions or dimpling (due to fixation to the pectoral muscles, deep fascia, Cooper ligaments, and/or overlying skin)
  • Peau d’orange (see below)

Subtypes and variants

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Inflammatory conditions (DDx)

• Mastitis
• Mammary duct ectasia
• Fat necrosis of the breast

Paget disease of the breast

• Definition: a rare type of breast cancer that affects the lactiferous ducts and the skin of the nipple and areola
• Pathogenesis: migratory/epidermotropic theory: neoplastic ductal epithelial cells from an underlying DCIS or IDC move through the lactiferous ducts and invade the surrounding epidermis of the nipple.
• Clinical features
  • Erythematous, scaly, or vesicular rash affecting the nipple and areola
  • Pruritus; burning sensation
  • Nipple retraction
  • Ulceration that causes blood-tinged nipple discharge
• Diagnostics
  • Punch/wedge or surface biopsy of nipple tissue: Paget cells confirm disease.

Inflammatory breast cancer (IBC)

• Definition: a rare form of advanced, aggressive invasive carcinoma characterized by dermal lymphatic invasion of tumor cells
• Clinical features
  • Peau d’orange
    • Erythematous, warm, and edematous skin plaques with prominent hair follicles that resemble orange peel
    • Caused by obstruction of the lymphatic channels due to tumor growth
  • Tenderness, burning sensation
  • Blood-tinged nipple discharge
  • Signs of metastatic disease (e.g., axillary lymphadenopathy)
  • Usually no palpable mass
• Differential diagnosis
  • Mastitis
    • Fever
    • No Peau d’orange
    • Good response to antibiotics
  • Paget disease of the breast
  • Breast abscess

Tip

It is called inflammatory breast cancer because its appearance resembles inflammation, but there is actually no inflammation!

Diagnostics

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Receptor testing

• Hormone receptors (HR) positive
  • Estrogen receptor
  • Progestogen receptor
• Human epidermal growth factor receptor 2 (HER2/neu, c-erbB2) positive
• Triple negative

Prognosis

• Hormone-negative breast cancer has a poorer prognosis than hormone-positive breast cancer.
• HER2-positive tumors show aggressive growth and metastasize quickly compared to HER2-negative tumors.
• Triple-negative disease is associated with a poor prognosis.

Treatment

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Systemic therapy

ERBB2-targeted therapy (ERBB2 = HER2)

ERBB2-targeted therapy includes ERBB2 antibodies (e.g., trastuzumab, pertuzumab) and tyrosine kinase inhibitors (e.g., lapatinib, neratinib).

• Indication: all ERBB2+ tumors
• First-line agent: trastuzumab
  • A humanized monoclonal antibody against the ERBB2 tyrosine kinase receptor; used in the treatment of ERBB2+ breast and gastric cancer
  • Mechanism of action: targets c-erbB2 tyrosine kinase receptor → ↓ of ERBB2-initiated cellular signaling and ↑ antibody-dependent cytotoxicity → ↓ tumor growth
  • Adverse effects: cardiotoxicity (e.g., dilated cardiomyopathy with systolic CHF)