Aziz, Zeba

10513 Background: Prior reports of high frequency of BRCA1 and BRCA2 ( BRCA1/2 ) PVs among South Asian women from Bangladesh, India, Nepal, and Pakistan with breast or ovarian cancer require validation in large prospective unselected cohorts. Methods: Individual-level anonymized patient data from two prospective cohorts were pooled to evaluate the prevalence of germline PVs among South Asian women: the South Asian Regional Alliance for Hereditary Cancers (SARAH Consortium) in Bangladesh, Nepal, and Pakistan, and the previously reported Nurse-led Genetic Counseling and Awareness (NuGenA) expansion cohort in India. Both studies enrolled consecutive cases of histologically confirmed newly diagnosed breast or epithelial ovarian cancer irrespective of age at diagnosis or family history. In both studies, participants completed questionnaires on personal and family history (first-, second- or third-degree) and provided blood for germline genetic testing after written consent. PVs in cancer predisposition genes including ATM, BARD1, BRCA1, BRCA2, BRIP1, CHEK2, MLH1, MSH2, MSH6, PALB2, RAD51C, RAD51D, and TP53 were identified as part of the studies utilizing a multigene panel and the results were returned to ordering clinicians. The data cutoff date for this analysis was November 30, 2025. Results: The analysis included 1,711 South Asian women with breast (n=1,210) or ovarian (n=501) cancer. A family history of breast or ovarian cancer was noted in 177 (10.3%). Among breast cancers, 94% were invasive, 84% were ductal, 35% were triple-negative and over two-thirds presented with nodal involvement. Germline PVs across 13 predisposition genes were observed in 17.7% of breast and 35.9% of ovarian cancers. Notably, BRCA1/2 PVs accounted for most of these PV (13.6% of breast and 28.3% of ovarian cancer cases) with PVs in all genes except BRCA1/2 under 1%. The frequency of BRCA1/2 PVs was 24.4% in triple-negative breast cancer and 8.0% in ER+/HER2-. BRCA1/2 PV carriers were diagnosed with breast cancer at a younger age than non-carriers (Median age: 42 vs 46 years, P<0.001), with no age difference observed in ovarian cancer (50 vs. 51 years, P=0.79). Notably, among the 306 BRCA1/2 PV carriers identified, 229 (74.2%) did not report a family history of breast or ovarian cancer. Conclusions: We confirm a high prevalence of BRCA1/2 PVs among unselected South Asian women with either breast or ovarian cancer. The observations of younger age at cancer diagnosis, and low rates of family history support the need for population-specific germline genetic testing and risk management strategies in South Asia.

Abstract Background: Ovarian cancer is the sixth leading cause of cancer deaths among women in the United States. South Asians in the USA, including Asian Indians and Pakistani Americans (AIPA), are a rapidly growing yet under-researched group. This study aims to analyze the clinical features, survival rates, treatment, and outcomes of ovarian cancer among AIPA women in the United States. Methods: Adult women diagnosed with ovarian cancer between 2000 and 2023 within the Surveillance, Epidemiology, and End Results (SEER) registry were identified utilizing ICD codes. The analysis focused on comparing clinical characteristics and outcomes between AIPA and Non-Hispanic White (NHW)women and excluded all women of other races/ethnicities or unknown race/ethnicity. Baseline characteristics, including age at diagnosis, disease stage, and treatment, were compared between AIPA and NHW women utilizing a chi-squared test for categorical variables and a t-test for continuous variables. The 5-year overall survival (OS) was estimated for each race/ethnicity by the Kaplan-Meier method, and the OS was further compared between AIPA and NHW in a cox-proportional hazard regression analysis adjusting for age at diagnosis, grade, histology, TNM stage, surgical debulking, completeness of debulking surgery, and receipt of chemotherapy. Similar comparisons of baseline characteristics and OS were also performed in the subset of women with high-grade serous ovarian cancer (HGSOC). Result: A total of 86, 485 women met the inclusion criteria, of which 1, 179 were AIPA and 85, 306 were NHW. AIPA had a significantly younger median age at diagnosis compared to NHW women in the overall population (57 vs. 65 years, p&lt;0.001) and among 448 AIPA and 29, 677 NHW women with HGSOC (58 vs. 65 years, p&lt;0.001). Approximately two-thirds of women in both groups presented with Stage III or IV ovarian cancer at diagnosis and had a serous subtype of ovarian cancer. Similarly, after the exclusion of unknown grade, high-grade tumors accounted for more than two-thirds (75 vs. 72%) of the ovarian cancer cases in both groups. AIPA were more likely to undergo debulking surgery (85 vs. 80%, p&lt;0.001) and receive chemotherapy (77 vs. 72%, p&lt;0.001) compared to NHW women. The unadjusted 5-year OS for AIPA and NHW women were 56% vs. 43% in the overall population, and 53% vs. 41% among women with HGSOC, respectively. In multivariate analysis of the entire study population, AIPA women had a significantly better OS than NHW women (HR: 0.86, 95%CI: 0.79 - 0.94, p&lt;0.001). Among women with HGSOC, a similar trend of better OS was noted in multivariate analysis among AIPA women compared to NHW (HR: 0.88, 95%CI: 0.77 - 1.01, p=0.07), although this did not reach statistical significance. Conclusion: The younger age at diagnosis, along with a generally better prognosis, among AIPA women compared to NHW women, suggests a possible enrichment of DNA-repair gene alterations among AIPA women. Citation Format: Aditi Karki, Sumeet Kumar Yadav, Muhammad Rafiqul Islam, Raja Pramanik, Ramila Shilpakar Dangol, Zeba Aziz, Sandhya Pruthi, Maryam Shahi, Jamie N. Bakkum-Gamez, Scott H. Kaufmann, Fergus J. Couch, Siddhartha Yadav. Clinical characteristics and survival outcomes of ovarian cancer among South Asian women in United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7118.