A 55-year-old woman has a 3 cm breast mass. Biopsy shows infiltrating ductal carcinoma. Immunohistochemistry reveals: ER−, PR−, HER2−. FISH confirms HER2 non-amplification. The tumor's aggressive behavior compared to hormone-receptor positive subtypes is best explained by:
- A Predominant BRCA1 germline mutation causing defective homologous recombination with genomic instability ✓
- B Amplification of VEGF receptors promoting angiogenesis
- C Loss of E-cadherin function enabling epithelial-mesenchymal transition
- D Overexpression of BCL-2 inhibiting the intrinsic apoptotic pathway
Explanation
Triple-negative breast cancer (TNBC) has the highest frequency of BRCA1 germline mutations among breast cancer subtypes. BRCA1 normally participates in homologous recombination repair of double-strand DNA breaks; its loss results in genomic instability, accumulation of mutations, and a basal-like phenotype with high-grade histology and aggressive clinical behavior. While E-cadherin loss drives lobular carcinoma (not ductal), and BCL-2 overexpression is anti-apoptotic, neither explains the specific aggressive biology of TNBC as well as BRCA1-related genomic instability.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.