Ethnic and clinical differences in gBRCA and HRD mutated breast and ovarian cancers and their response to PARP inhibitors.

Abstract

e13102 Background: Hereditary mutations of the homologous recombination (HR), the key DNA double-strand break repair pathway, are one of the well-known causes of breast and ovarian cancers. Few reports exist on these mutations and the utilization of PARP inhibitors in the Middle Eastern region. Methods: This is a single-center retrospective study of breast and ovarian cancer patients who underwent genetic testing for g BRCA and HR defects (HRD) respectively between August 2021 and May 2023. Data was summarized using descriptive statistics and compared using counts and percentages. Response to treatment was assessed using RECIST criteria. Results: The prevalence of pathogenic mutations was 22.8%, with 26.3% of breast cancers harboring g BRCA mutations and 24% of ovarian cancers showing HRD positivity. Middle Eastern patients comprised 40% of the g BRCA-positive breast cancer group, while Asians accounted for 66% of the HRD-positive ovarian cancer patients. In mutated breast cancer, 53.3% had a positive family history of cancer. 33.3% of mutated breast cancer group and 66.6% of the ovarian cancer group received PARPis. Objective response to PARPi was 40% and 100% in breast and ovarian cancers, respectively. Conclusions: Our study revealed a high prevalence of g BRCA mutations (26.3%) in breast cancer and HRD positivity (24%) in ovarian cancer). Ethnic profiles differed between these cancers, with Middle Eastern and Southeast Asian patients dominating the breast and ovarian groups, respectively. Interestingly, the TNBC rate in breast cancer remained around 20% regardless of g BRCA status. While disparities between HRD groups were more pronounced in ovarian cancer, as expected, unexpected trends emerged in breast cancer. Further research with larger cohorts is needed to confirm these findings. [Table: see text]