Histopathological characterization of carcinoma breast with BRCA1/2 sequence variation in a Tertiary Care Center in Kerala, South India

Abstract

Background: Hereditary breast cancers constitute around 5%–10% of all breast cancers. The most commonly mutated genes in hereditary breast and ovarian cancer syndrome are the BRCA1 and BRCA2 genes. There has not been any research into the histopathological features of BRCA1/2 mutations in breast cancer in Kerala. The goal of this work was to use next-generation sequencing to look into the range of BRCA1/2 genetic variants and to discover characteristic histopathologic features associated with BRCA1/2 sequence variations. Methods: Fifty female patients diagnosed with carcinoma breast were screened for BRCA1/2 variants by next-generation sequencing. Patients were selected irrespective of age or family history of breast or ovarian cancer. The histopathological features of BRCA1/2 associated breast cancer cases were also studied. Results: We identified sequence variants in BRCA1 and BRCA2 genes in 6 women (6/50, 12%). The sequence variants included two deleterious mutations and five variants of uncertain significance. It was observed that most of the patients with BRCA1/2 sequence variants presented with aggressive tumor characteristics. Statistical significance was noted in BRCA1/2 carriers with tumors of higher histologic grade (P = 0.048). Conclusion: Morphological and immunohistochemical features of BRCA1/2-associated breast cancer may be valuable to predict mutation carrier status for appropriate therapeutic decision-making.

Keywords

• brca1
• brca2
• histopathology
• immunohistochemistry
• pathogenic mutation
• variant of uncertain significance