Clinicopathologic characteristics and survival outcomes in adolescent and young adults with breast cancer.
Authors: Madeleine Turcotte, Cody Lebeck Lee, Margaret Comer, Sally Momoh, Heidi Chen, Lucy Spalluto, Tuya Pal, Sonya A. Reid
Journal: Journal of Clinical Oncology (2025)

e12508 Background: Breast cancer is the most common cancer and the leading cause of cancer-related death among adolescent and young adults (AYA) diagnosed between age 15-39. AYA with breast cancer have worse survival rates due to more aggressive tumor biology. The impact of non-biological factors on survival outcomes is not well defined among AYA with breast cancer. This study aimed to characterize clinicopathological characteristics and survival outcomes in AYA with breast cancer. Methods: We conducted a retrospective cohort study of all patients diagnosed with invasive breast cancer before age 40 between 2013-2023 at a tertiary medical center. Demographic and clinicopathological characteristics were obtained from the electronic medical record. For patients with Stage I-III breast cancer, we used univariate and multivariable Cox proportional hazards to analyze the association between clinicopathological characteristics and survival outcomes (disease free survival (DFS) and overall survival (OS)). Results: Our cohort included a total of 498 women (80% White, 10% Black, 5% Hispanic, 4% Asian, 1% Other). The median age at diagnosis was 36 years (IQR, 32-38). Most patients presented with localized disease (23% Stage 1, 48% Stage 2, 23% Stage 3, 6% Stage 4) with over-representation of HER2+ (27%) and triple negative breast cancer, TNBC (23%). Most patients had high-grade tumors (54%), lymph node involvement (49%) and received neoadjuvant chemotherapy (54%). 53% of patients had a family history of breast and/or ovarian cancer. Of the 92% who received germline testing,18% had a germline mutation in a moderate/high penetrant gene (35% BRCA1 , 22% BRCA2 , 7% PALB2 , 7% TP53 , 13% ATM , 15% CHEK2 ). The 4-yr DFS was 68% and 4-yr OS was 80%, with a median follow up of 4.1 years (IQR, 2.3-7.1). In multivariable analysis, Stage III disease was independently associated with worse DFS (HR 1.8, 95% CI 1.1-2.9) and OS (HR 2.0, 95% CI 1.1-3.8), after adjusting for potential confounders. TNBC trended towards worse DFS (HR 1.4, 95% CI 0.8-2.5) and was significantly associated with worse OS (HR 2.5, 95% CI 1.1-6.0). A non-significant trend towards worse DFS (HR 1.7, 95% CI 0.9-3.1) and OS (HR 1.7, 95% CI 0.8-3.8) was seen in Black women. Conclusions: Our findings highlight the over-representation of aggressive clinicopathological characteristics, disproportionately high mortality burden, and racial survival disparities in AYA with breast cancer. We also found a high prevalence of germline mutations underscoring the need for increased utilization of breast cancer risk-assessment tools to identify young individuals at high risk for breast cancer who may benefit from personalized screening strategies to facilitate early detection and improve survival in this vulnerable population. Furthermore, there remains an urgent need to develop tailored management guidelines to address the unique challenges faced by AYA with breast cancer.