Abstract B014: Early-onset breast cancer and reproductive timing: results from the Mexican Teachers’ Cohort

Abstract Background: The incidence of early-onset breast cancer (EOBC; diagnosed under the age of 50) is rising globally, with incidence and mortality rates in Latin America being twice as high as those in high-income countries. The Mexican Teachers’ Cohort, the largest prospective cancer study in the region, is uniquely positioned to provide valuable insights into EOBC in Latin America. Methods: We followed 95,828 Mexican women younger than 50 (2006–2023; 824,053 person-years). Incident breast cancers were validated through population-based cancer and mortality registries, health utilization datasets (Positive predictive value, PPV, 97%), and self-reports. EOBC was defined as a diagnosis <50 years. For each reproductive factor (age at menarche, parity/number of births, age at first full-term pregnancy (FFTP), breastfeeding, and hormonal contraceptive (HC) use), we used multivariate Cox proportional hazards models with follow-up time as the time scale to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Adjustment sets were selected a priori using directed acyclic graphs (DAGs). Results: Among 2,214 incident breast cancers, 618 were EOBC, <50 years old (28%): 47 occurred before 40, 160 between 40–44, and 411 between 45–49 years. In EOBC-focused models, later menarche was inversely associated with EOBC incidence (per-year HR, 0.93; 95% CI, 0.88–0.98; ≥15 vs. ≤11 years, HR, 0.72; 95% CI, 0.53–0.98). Having had a full-term birth showed no clear protective effect (HR, 0.97; 95% CI, 0.77–1.22). Among women who have given birth, higher parity was protective (3 vs. 1 birth: HR 0.67, 0.51–0.88; 4 or more vs. 1: HR 0.85, 0.62–1.18; per additional birth: HR 0.92, 0.84–1.01). Older age at first FFTP was linked to higher EOBC incidence compared to age 19 or younger (20–24 HR 1.24, 0.85–1.79; 25–29 HR 1.21, 0.83–1.76; 30–34 HR 1.53, 1.01–2.31; 35 or older HR 1.58, 0.89–2.82; per year HR 1.02, 1.00–1.04). Breastfeeding showed no strong protective effect, with some modest inverse estimates without a clear dose–response relationship (≥18 vs 0 months: HR 0.82, 0.59–1.14; per additional month: HR 0.99, 0.98–1.00). HC use was positively associated with EOBC (ever vs never, HR 1.22, 1.04–1.45); use of ≥5 years showed a similar trend (HR 1.25, 0.99–1.57). Oral HC users had a higher incidence of EOBC compared to non-users (HR 1.27, 1.04–1.55). Conclusions: In this cohort, one-third of breast cancer diagnoses occur before the age of 50. The timing of reproductive events—specifically, later onset of menarche (which appears to be protective), older age at FFTP, and higher parity (also protective)—was noted. At the same time, there is limited evidence supporting the protective role of breastfeeding and only modest positive associations identified with certain patterns of hormonal contraceptive use. These findings, derived from an underrepresented population, underscore the importance of incorporating reproductive timing into risk stratification and prevention strategies for EOBC in Mexico and throughout Latin America. Citation Format: Liliana Gomez-Flores-Ramos, Leticia Palma, Dalia Stern, Marion Brochier, Jocelyn Jaen, Adrian Cortes, Alberto Castellanos, Martin Lajous. Early-onset breast cancer and reproductive timing: results from the Mexican Teachers’ Cohort [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl):Abstract nr B014.

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