Abstract PL04-02: Young-onset breast cancer: Lessons learned from postpartum diagnoses

Abstract Compared to postmenopausal breast cancer, young onset breast cancer (YOBC) is increasing in incidence, is less responsive to standard-of-care therapies, and has poorer prognosis even after controlling for tumor biologic subtype and stage. Further, contrary to expectations, more young patients die from ER-positive than ER-negative disease, necessitating increased focus on ER-positive YOBC. With respect to increasing incidence, several population-level changes to hormone exposure are predictive of elevated risk, including decreased age at menarche, delayed childbearing, and decreased breastfeeding duration. However, causality remains unknown and alternative hypotheses are warranted. With respect to improved outcomes for young patients, unmet needs include a lack of understanding of the proclivity for metastasis and the mechanisms of therapy resistance. Importantly, insights based on normal mammary gland biology have led to major breakthroughs in our understanding of YOBC, including: 1. Our current understanding of postpartum breast involution as a wound-like process that facilitates tumor growth, immune avoidance, hormone refractory disease, and early-stage shedding. 2. The identification of the breast-liver axis during a reproductive cycle that establishes a premetastatic niche in the postpartum liver. These newly described postpartum biologies provide a construct to better understand poor prognosis in YOBC, highlight the role of tumor extrinsic factors in driving metastasis, and provide new strategies for prevention, prognosis, and treatment of YOBC. Citation Format: Pepper Schedin. Young-onset breast cancer: Lessons learned from postpartum diagnoses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr PL04-02.