Breast cancer

Breast cancer is commonly found in postmenopausal women, often presenting as a hard, palpable mass, typically in the upper outer quadrant of the breast. Advanced invasive cancers may become fixed to deeper structures, such as pectoral muscles, deep fascia, Cooper’s ligaments, or the overlying skin, leading to nipple retraction or skin dimpling.

Key Features

Origin: Usually arises from the terminal duct lobular unit.
Receptor Amplification: Overexpression of estrogen/progesterone receptors or HER2 (c-erbB2, an EGF receptor) is common.
Triple Negative Cancer: Lacks ER, PR, and HER2 receptors; tends to be more aggressive.

Risk Factors

In Women

Age: Higher risk in older age groups.
History of Atypical Hyperplasia: Increased risk of malignancy.
Family History: Close relatives with breast cancer increase susceptibility.
Genetic Mutations: BRCA1/BRCA2 mutations.
Race: There is a higher risk in Caucasians, with African Americans at greater risk for triple-negative cancers.
Increased Estrogen Exposure: Factors like nulliparity, postmenopausal obesity, high menstrual cycle count, lack of breastfeeding, and late first pregnancy.
Alcohol Intake: Known to increase risk.

In Men

BRCA2 Mutation
Klinefelter Syndrome

Prognostic Factor

Axillary Lymph Node Metastasis: The most crucial prognostic factor in early-stage disease.

Types of Breast Cancer

Type	Characteristics	Notes
Noninvasive Carcinomas
Ductal Carcinoma In Situ (DCIS)	Fills the ductal lumen, seen as microcalcifications on mammography.	Early malignancy without basement membrane invasion; may have necrosis and calcification.
Comedocarcinoma (Subtype of DCIS)	High-grade cells with central necrosis and dystrophic calcification.	A subtype with extensive central necrosis.
Paget Disease	Extension of DCIS/invasive cancer into nipple, presenting as eczematous patches.	Associated with intraepithelial adenocarcinoma cells (Paget cells).
Lobular Carcinoma In Situ (LCIS)	Lacks E-cadherin, no mass or calcifications; often found incidentally.	Increases risk of cancer in either breast.
Invasive Carcinomas
Invasive Ductal	“Rock-hard” mass with sharp margins and duct-like cells within a desmoplastic stroma.	Most common form of invasive breast cancer.
Invasive Lobular	Cells in an orderly row (“single-file” pattern), lacks E-cadherin and often lacks duct formation.	Tends to be bilateral with multiple lesions in the same location.
Medullary	Anaplastic cells growing in sheets with lymphocytes and plasma cells, may mimic fibroadenoma.	Has a well-circumscribed appearance.
Inflammatory	Dermal lymphatic invasion, presenting as painful, warm, swollen, and erythematous skin (peau d’orange).	Poor prognosis, often mistaken for mastitis or Paget disease, and usually lacks a mass.

Points to Remember

Axillary lymph node involvement is crucial for prognosis.
Triple-negative cancers (ER-/PR-/HER2-) are aggressive and more challenging to treat.
Inflammatory breast cancer has a poor prognosis and is often misdiagnosed due to its skin appearance.
Receptor status (ER, PR, HER2) guides treatment options and helps predict disease progression.

Study Tips for USMLE Step 1

Focus on memorizing common risk factors and presenting symptoms.
Know the histological differences between types of breast cancer.
Understand the significance of receptor status in guiding prognosis and treatment.
Be familiar with clinical presentations like peau d’orange for inflammatory breast cancer and Paget’s disease for DCIS.

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