Abstract PS5-12-08: Survival Outcomes and Tumor Site Distribution by Molecular Subtype in Breast Cancer Patients Under 40

Abstract Background Screening guidelines for breast cancer typically begin at age 40, leaving younger women at risk for delayed detection. The survival outcomes and tumor site patterns by subtype in this younger population remain underexplored. Our analysis leverages comprehensive national data to fill this critical knowledge gap, offering one of the most detailed evaluations to date of molecular subtype distribution, prognostic disparities, and anatomical presentation in women under 40. Methods Using the SEER 18 registry, we identified 5,026 female patients diagnosed under age 40 with invasive breast cancer in 2018. This year was selected for the most recent data available on SEER with its complete molecular subtype, staging, and anatomical site information. Breast cancer subtypes were categorized as Luminal A (HR+/HER2−), Luminal B (HR+/HER2+), HER2-Enriched (HR−/HER2+), and Triple-Negative (HR−/HER2−). We stratified patients into four age groups (15-29, 30-39, 40-44, 45-49) and used Chi-square tests to assess distributional differences. Kaplan-Meier curves estimated 5-year cancer-specific survival by subtype, with log-rank tests for comparison. Multivariable Cox models, random survival forests, and Mahalanobis distance matching estimated prognostic outcome and treatment effects. ICD-O-3 topography codes (C50.0-C50.9) were used to analyze tumor primary site distributions across subtypes. Results Among women under 40 with breast cancer, Luminal A was the most common subtype (52.6%), followed by Triple-Negative (18.5%), Luminal B (17.0%), HER2-Enriched (6.1%), and unclassified (5.9%). Younger women presented more often with metastatic disease and had lower rates of localized tumors than women over 40 (5.0% and 60.2%, respectively). Luminal B demonstrated the highest 5-year survival probability in the case of young women, followed by Luminal A, HER2-Enriched, URNA, and Triple-Negative, which had the poorest prognosis (log-rank p < 0.0001), whereas Luminal A showed better survival in patients above 40. Black women under 40 had the highest rate of Triple-Negative cancers (22.6%) compared to 20.6% for Hispanic, 18% for Non-Hispanic White, and 12% for other. White/non-Hispanic and other (including Asian) women have a higher percentage of cases diagnosed as Luminal A (53.3% and 58.4%) to 49.3% for Black and 50.2% for Hispanic. Additionally, lower-income women under 40 had more aggressive subtypes and poorer survival than higher-income groups. Those living in rural areas also face significantly worse outcomes than those living in urban metros. The most common tumor site was the upper-outer quadrant (33.0%), especially in Luminal subtypes, followed by overlapping lesions (C50.8, 22.6%) and breast, NOS (C50.9, 14.8%). While Triple-Negative and HER2-Enriched tumors were more often in overlapping or non-specific locations (p < 0.0001). Conclusions Breast cancer in women under 40 presents distinct biological behavior, survival patterns, and tumor site distributions by subtype. The favorable prognosis of Luminal B tumors highlights the impact of targeted therapies and supports aggressive, subtype-specific treatment in young patients. In contrast, poorer outcomes among young women with Luminal A tumors suggest even traditionally low-risk subtypes require close monitoring. Triple-Negative disease remains the most lethal, emphasizing the urgent need for novel therapies and clinical trial inclusion. Subtype-related differences in tumor localization may inform imaging and surgical strategies. Our findings highlight the need for earlier detection strategies, personalized management approaches that consider tumor subtype biology, genetic risk, and fertility concerns in this high-risk population. Citation Format: M. Noorani, S. Goyal, S. Viduarri, A. Calderon, C. Pham, S. Singh, A. Dhasmana, S. Dhasmana, M. Yallapu, S. C. Chauhan, D. Nguyen, S. Fofana, S. Khan. Survival Outcomes and Tumor Site Distribution by Molecular Subtype in Breast Cancer Patients Under 40 [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-12-08.