Gynecologic and breast cancers with hereditary cancer predisposition syndromes

Abstract

Approximately 20–25% of ovarian cancers, 5–10% of uterine cancers, and 5–10% of breast cancers are attributable to inherited pathogenic genetic alterations. Identifying characteristic germline mutations is crucial for patient management, as appropriate surveillance and further surgical interventions for risk-reduction may be considered in such groups. Hereditary breast and ovarian syndrome (HBOC) are characterized by inherited pathogenic germline mutations, the majority of which are attributable to pathogenic BRCA1 or BRCA2 variants, among many other genes including MMR genes, TP53, PTEN, PALB2, ATM and BARD1, etc. These cases often have distinctive morphological and immunohistochemical characteristics, which when recognized by the pathologist may encourage further genetic consultation and testing for the patient. BRCA1/2-associated carcinomas display more aggressive pathologic features than their sporadic counterparts. High-grade serous carcinoma is the most predominant type of ovarian neoplasm in BRCA1/2 variant-associated cases, with often solid, pseudo-endometrioid, or transitional (SET) morphologic pattern. BRCA1-associated breast cancer more frequently exhibits a medullary pattern with prominent tumor infiltrating lymphocytes (TILs) and a triple-negative phenotype. BRCA2-associated tumors in comparison have a more heterogenous histologic phenotype. This article reviews the histopathologic features of hereditary gynecologic and breast cancer syndromes and discusses surveillance and surgical considerations for these patients.