Treatment delay and survival in patients with breast cancer by stage and cardiovascular comorbidity: a nationwide Korean cohort study

The impact of treatment delay on breast cancer survival across disease stages remains inconsistent across studies. We evaluated the association between time to treatment initiation (TTI) and overall survival by disease stage among Korean women with breast cancer. A retrospective cohort study was conducted using the Breast Cancer Collaborative Stage-Linked Database (2012–2019), established under the Korean Clinical Data Utilization for Research Excellence (K-CURE) project. TTI was categorized as ≤ 30 days (reference), 31–60 days, ≥ 61 days, or no treatment within 1 year. Stage-stratified Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for overall survival. Subgroup and interaction analyses were performed according to molecular subtype and comorbidity status. A total of 16,495 women were included. Among treated patients, TTI was not significantly associated with overall survival in stage I, II, or IV disease. In stage III disease, a TTI of ≥ 61 days was associated with a higher hazard of death (aHR, 1.50; 95% CI 1.04–2.16). A TTI of ≥ 61 days was also associated with a higher hazard of death among patients with triple-negative breast cancer (aHR, 1.75; 95% CI 1.10–2.78) and HR+/HER2 + tumors (aHR, 1.41; 95% CI 1.04–1.92). Overall interaction tests did not show significant heterogeneity by disease stage or molecular subtype ( P = 0.72 and 0.58, respectively). The overall TTI-by-CVD interaction was not statistically significant ( P = 0.48). However, in exploratory stage-specific analyses, a TTI-by-CVD interaction was observed in stage III disease ( P = 0.015), with an aHR of 5.28 (95% CI 1.78–15.68) among patients with preexisting CVD and 1.30 (95% CI 0.86–1.97) among those without CVD. TTI ≥ 61 days was associated with higher mortality in stage III breast cancer and in TNBC and HR+/HER2 + subgroups. Findings regarding CVD should be considered exploratory and require confirmation in larger studies.