A breast tumor is ER-negative, PR-negative, and HER2-negative (triple-negative breast cancer, TNBC). Genomic profiling shows a BRCA1 germline mutation. What is the histological subtype most commonly associated with BRCA1-mutated TNBC and its characteristic molecular profile?
- A Invasive lobular carcinoma with loss of E-cadherin
- B Invasive ductal carcinoma, NOS with high-grade nucleus and central necrosis; basal-like subtype (CK5/6+, EGFR+) ✓
- C Mucinous (colloid) carcinoma with favorable prognosis
- D Tubular carcinoma with low-grade histology and E-cadherin retention
Explanation
BRCA1-associated breast cancers are predominantly high-grade invasive ductal carcinomas of the basal-like subtype (one of the intrinsic subtypes defined by gene expression profiling). They characteristically express basal markers (CK5/6, CK14, EGFR/CK17), are ER/PR/HER2-negative (triple-negative), show high mitotic rate, pushing tumor margins, lymphocytic infiltrate, central necrosis/fibrosis, and a medullary-like pattern. BRCA1 normally participates in homologous recombination (HR) DNA repair — its loss leads to genomic instability. These tumors are sensitive to platinum agents and PARP inhibitors due to HR deficiency.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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