Abstract PS4-05-01: Postpartum Associated Breast Cancer and Its Survival Impact among Young Women

Abstract Background: Over half of women diagnosed with breast cancer (BC) before the age of 45 fall within the postpartum window, generally defined as a diagnosis made up to 10 years after last delivery. Postpartum has been associated with poorer outcomes and may be a key determinant of the worst prognosis described among young BC patients. Diagnostic delays and biological changes in tumor microenvironment could explain this increased risk. Moreover, delayed childbearing can intensify the postpartum risk and forestall the long-term protective effects of pregnancy. We herein present a retrospective analysis of postpartum-associated BC (PPBC) from a single institution. Methods: Retrospective analysis including a cohort of 223 women under 45 years diagnosed at the Hospital Clinic of Barcelona (2010-2023) with complete pregnancy history. Patients were stratified into PPBC (n=113) defined as BC diagnosed postpartum and up to 10 years after last delivery, and non-PPBC (n=110), either nulliparous or diagnosed after 10 years of last delivery. Analyses evaluated disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) in early-stage patients. Subgroup analyses in PPBC explored the effect of time since delivery (5 vs. ≥5-10 years) and age at first pregnancy (≤30 vs. 30 years). PAM50/PROSIGNA was used to determine intrinsic subtypes and risk of recurrence (ROR). Clinicopathological features and survival outcomes were analysed using Chi-square tests, Kaplan-Meier, and Cox regression models. Results: PPBC cases were slightly older at diagnosis than non-PPBC (median 38.0 vs. 36.8 years, p=0.017). Stage distribution was similar, though stage IV disease at diagnosis was numerically higher in PPBC (9.7% n=11 vs. 5.5% n=6, p=0.262). Immunohistochemistry (IHC)-based subtypes were comparable (p=0.857), with 59.3% of PPBC and 57.3% of non-PPBC patients having estrogen receptor-positive /HER2-negative (ER+/HER2−) subtype. No other significant differences were observed regarding tumor size, nodal status, histologic type or grade, or Ki67 index. Among patients with available PROSIGNA (n=65; 35 PPBC and 30 non-PPBC), no significant differences for intrinsic subtypes (p=0.892) or ROR categories (p=0.344) were found. At a median follow-up of 85 months, 7-year DFS and DDFS were numerically lower in PPBC compared to non-PPBC (DFS: 75.1% vs. 83.3%; DDFS: 76.2% vs. 89.5%), though only DDFS approached statistical significance (hazard ratio HR 1.90, 95% CI 0.976-3.702; p=0.054). Noteworthy, OS was significantly reduced in PPBC patients (7-year OS: 89.6% vs. 95.6%; HR 3.01, 95% CI 1.00-9.79; p=0.042), with persisting differences in the full cohort including de novo stage IV cases (HR 3.4, 95% CI 1.23-9.38; p=0.01). Within PPBC, those diagnosed 5 years postpartum had numerically worse DFS (HR 1.72, 95% CI 0.84-3.53; p=0.136), while no survival differences were observed by age at first pregnancy (p=0.610). In multivariate Cox regression models excluding metastatic cases and adjusting for age at diagnosis, tumor size (cT 2-4 vs. 1), nodal status (cN 1-2 vs. 0), and IHC subtype, PPBC was independently associated with worse DFS (HR 2.63, 95% CI 1.18-5.89; p=0.019) and DDFS (HR 2.82, 95% CI 1.24-6.45; p=0.014). Tumor size was also an independent predictor of recurrence across all models. Regarding OS, PPBC remained an independent risk factor (HR: 6.96 95% CI 1.58-30.71; p=0.010), while increasing age was associated with better survival (HR: 0.81 95% CI 0.68-0.96; p=0.018). Conclusions: PPBC is an independent predictor of poor survival among young women. In the absence of differences in clinical stage or tumor subtype, these findings suggest that postpartum-specific biological mechanisms may underlie the worse outcomes observed. Further investigation is needed to refine risk stratification and improve care in this distinct population. Citation Format: B. WalbaumA. MorellJ. Muñoz-CarrilloL. ArenasA. Del ValM. ReyP. Gimenez-XavierN. ChicF. Brasó-MaristanyE. SeguiR. Gómez-BravoI. García-FructuosoT. PascualF. SchettiniM. BergaminoM. González-RodríguezB. AdamoM. MuñozE. SanfeliuA. PratO. Martínez-SáezM. Vidal. Postpartum Associated Breast Cancer and Its Survival Impact among Young Women 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 PS4-05-01.