[Hereditary breast carcinomas pathologist's perspective].

Area of Science:

• Oncology
• Genetics
• Pathology

Background:

• Hereditary mutations in genes like BRCA1/2 account for 5-10% of breast cancers.
• PARP inhibitors are now approved for BRCA1/2-mutated breast cancer patients.
• Morphological identification of specific tumor characteristics could streamline genetic testing.

Purpose of the Study:

• To explore morphological and phenotypic features of hereditary breast cancers.
• To identify potential indicators for genetic mutation screening.
• To facilitate patient care and targeted therapy selection.

Main Methods:

• Review of histopathological and phenotypic characteristics of breast cancers associated with various hereditary mutations (BRCA1, BRCA2, TP53, PTEN, CDH1, etc.).
• Analysis of established criteria (e.g., Chompret criteria) for accelerating genetic analysis.
• Discussion of potential immunohistochemical markers (e.g., RAD51) and future AI applications.

Main Results:

• BRCA1-mutated cancers often present as high-grade, triple-negative invasive carcinomas with lymphocytic infiltration.
• BRCA2 and other associated mutations (CHECK2, PALB2, etc.) typically show grade III, luminal B invasive carcinomas.
• Specific morphologies like HER2-amplified or triple-negative tumors in younger women can prompt genetic testing.

Conclusions:

• Certain morphological and phenotypic features can suggest hereditary breast cancer, aiding pathologists in guiding genetic analysis.
• Current morphological sorting is limited to specific criteria (e.g., triple-negative <50 years, HER2-amplified <31 years).
• RAD51 immunohistochemistry and AI-driven analysis of digital slides hold promise for improved identification of hereditary breast cancers and PARP inhibitor sensitivity.