BRCA1-associated breast cancers characteristically show triple-negative (ER-/PR-/HER2-) phenotype. Compared with sporadic breast cancer, BRCA1 tumors are more commonly of which histological grade and subtype?

• A Grade 3 (poorly differentiated) invasive ductal carcinoma, often with medullary features ✓
• B Grade 1 (well-differentiated) invasive lobular carcinoma
• C Phyllodes tumour with stromal overgrowth
• D Grade 2 mucinous carcinoma with intracellular mucin pools

Explanation

BRCA1-associated breast carcinomas are characteristically high-grade (Grade 3), ER-negative, PR-negative, HER2-negative (triple-negative/basal-like subtype), with features overlapping medullary carcinoma: pushing borders, syncytial growth pattern, lymphocytic stroma, and high mitotic index. BRCA2-associated cancers more closely resemble sporadic ER-positive, HER2-negative cancers. Invasive lobular carcinoma characteristically lacks E-cadherin and is associated with CDH1 mutations, not BRCA1. Phyllodes tumours are biphasic stromal-epithelial tumours.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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