Co-Pathogenic Role of BRCA1 and OBSCN Deletions in Chinese Familial Breast Cancer: A Case Report

BACKGROUND The incidence of breast cancer is high among women, with a significant proportion of cases being familial. However, the driver genes for breast cancer can differ across families. CASE REPORT Our patient was a 37-year-old woman diagnosed with triple-negative breast cancer (TNBC) by pathology, revealing invasive ductal carcinoma of the outer upper quadrant of the breast, WHO grade 3. The maximum diameter of the microscopic invasive cancer was approximately 0.5 cm. No definite vascular tumor thrombus or nerve invasion was observed. Some (30-90%) of the tumor cells disappeared, and the remaining tumor cells showed degeneration, interstitial sclerosis, scattered lymphocyte infiltration, and hemosiderin deposition. No cancer was found in the nipple and base resection margins, or in the other quadrants. The chemotherapy response was classified as grade III according to the MP (Miller and Payen classification) scoring system. Blood samples were collected from affected family members. Whole-exome sequencing (WES) and bioinformatics analyses were used to identify potential driver genes, followed by Sanger sequencing for validation, which ultimately confirmed the pathogenic gene and the underlying mechanism in this family. CONCLUSIONS A series of analyses suggested that the co-occurrence of heterozygous deletions in BRCA1 and OBSCN was the main cause of breast cancer in this family. The simultaneous association of 2 genes with the occurrence of breast cancer was discovered for the first time in this family, which could help guide disease prevention for family.