Abstract Background: Timely initiation of adjuvant endocrine therapy (AET) is a quality metric in hormone receptor-positive (HR+) breast cancer, but real-world data on optimal timing post-surgery are limited. We evaluated recurrence outcomes among patients initiating AET early (≤12 weeks) vs delayed (≥12 weeks) after surgery. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, which includes de-identified electronic health records from 146 healthcare organizations across the world. Women aged ≥18 years with Stage I-II HR+/HER2-negative breast cancer who underwent surgery and initiated adjuvant endocrine therapy were eligible. Surgery included partial mastectomy (e.g., lumpectomy, quadrantectomy), mastectomy with axillary lymphadenectomy, and simple mastectomy. Two cohorts were defined: Early AET Group: AET initiated within ≤12 weeks post-surgery (n=5,793) and Delayed AET Group: AET initiated after ≥12 weeks post-surgery (n=9,982).The primary outcome was breast cancer recurrence, defined using ICD-10 codes C77 (secondary neoplasm of lymph nodes) and C79 (secondary neoplasm of other sites), measured from 1 to 5 years after AET initiation. A multivariable Cox proportional hazards model estimated adjusted hazard ratios (aHRs) for recurrence, adjusting for age, disease stage, receipt of chemotherapy, Ki-67 status, and comorbidities (diabetes, chronic kidney disease CKD, and coronary artery disease CAD). Results: A total of 15,842 patients were included: 5,810 in the Early AET group and 10,032 in the Delayed AET group. In univariate analysis, early AET was associated with a significantly lower risk of recurrence (HR 0.891, 95% CI: 0.799-0.992; p = 0.035). After adjusting for covariates in a multivariable model, early AET initiation remained independently associated with reduced recurrence (adjusted HR 0.891). Other significant predictors of increased recurrence included stage 2 disease, chemotherapy, diabetes mellitus, and coronary artery disease. Age was inversely associated with recurrence. Ki-67 and CKD were not significantly associated with recurrence. Conclusions: Initiating adjuvant endocrine therapy within 12 weeks post-surgery is associated with a significant reduction in recurrence among HR+/HER2-negative breast cancer patients. These findings reinforce the adoption of early AET initiation as a key quality metric in breast cancer care. Citation Format: S. Afridi, K. Doshi, Z. Shah, S. Gandhi. Early (≤12 weeks) vs Delayed (≥12 weeks) Initiation of Adjuvant Endocrine Therapy After Surgery on Recurrence in HR+ Breast Cancer: A Real-World Global Cohort Study 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 PS1-11-14.
Afridi et al. (Tue,) studied this question.