Treatment delays raise death risk in stage III breast cancer, Korean cohort finds

Women with stage III breast cancer whose treatment began more than 60 days after diagnosis faced a roughly 50 percent higher risk of death compared with patients who started treatment within 30 days, according to a nationwide retrospective cohort study from South Korea. The study, published in Breast Cancer Research, drew on the Breast Cancer Collaborative Stage-Linked Database covering 2012 to 2019, established under the Korean Clinical Data Utilization for Research Excellence (K-CURE) project, and included 16,495 women with breast cancer.

The researchers categorized time to treatment initiation (TTI) as 30 days or fewer, 31 to 60 days, 61 days or more, or no treatment within one year, and used stage-stratified Cox proportional hazards models to estimate adjusted hazard ratios for overall survival. Among patients who received treatment, TTI was not significantly associated with overall survival in stage I, stage II, or stage IV disease. Only in stage III disease did the longest delay category show a significant association, with an adjusted hazard ratio of 1.50 (95 percent confidence interval 1.04 to 2.16) for a TTI of 61 days or more.

Subgroup analyses by molecular subtype revealed that the longest treatment delays were also linked to higher mortality in specific tumor types. Among patients with triple-negative breast cancer, a TTI of 61 days or more was associated with an adjusted hazard ratio of 1.75 (95 percent CI 1.10 to 2.78), while patients with HR-positive/HER2-positive tumors showed an adjusted hazard ratio of 1.41 (95 percent CI 1.04 to 1.92) in the same delay category.

However, formal interaction tests across the whole cohort did not show statistically significant heterogeneity in the delay-survival relationship by disease stage or by molecular subtype, with P values of 0.72 and 0.58 respectively. This means the stage- and subtype-specific findings should be interpreted with caution, as the overall data do not confirm that the effect of delay genuinely differs across these groups.

The study also examined whether preexisting cardiovascular disease (CVD) modified the relationship between treatment delay and survival. Across the entire cohort, the overall TTI-by-CVD interaction was not statistically significant (P = 0.48). In exploratory stage-specific analyses, however, the investigators observed a significant interaction in stage III disease (P = 0.015): among patients with preexisting cardiovascular disease, a TTI of 61 days or more was associated with an adjusted hazard ratio of 5.28 (95 percent CI 1.78 to 15.68), compared with an adjusted hazard ratio of 1.30 (95 percent CI 0.86 to 1.97) among patients without cardiovascular disease.

The authors emphasized that the cardiovascular disease findings should be considered exploratory and require confirmation in larger studies.

Methodologically, the retrospective cohort design links nationwide cancer registration data with treatment records, allowing stage-stratified analysis of a large population. Because the study is observational, the associations between treatment delay and mortality cannot be interpreted as definitive causal effects; factors such as disease aggressiveness, patient condition, and clinical decision-making may influence both the timing of treatment initiation and survival outcomes.

The finding that treatment delay showed no significant association with survival in early-stage or metastatic disease, while reaching significance only in stage III, adds nuance to a literature in which results have been inconsistent across studies. The authors note that the impact of treatment delay on breast cancer survival across disease stages has remained inconsistent in prior research, motivating their stage-stratified approach.

Overall, the study suggests that in this Korean nationwide cohort, delays of more than 60 days before starting treatment were associated with higher mortality specifically among women with stage III breast cancer and among patients with triple-negative or HR-positive/HER2-positive tumors, while the role of preexisting cardiovascular disease in modifying this risk remains an open question for future research.

Subject of Research: The association between time to treatment initiation and overall survival by stage and cardiovascular comorbidity in Korean women with breast cancer

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

Article References: Kim, H.-J., Baek, J. Y., Lee, K.-H., & Shin, A. (2026). Treatment delay and survival in patients with breast cancer by stage and cardiovascular comorbidity: a nationwide Korean cohort study. Breast Cancer Research. https://doi.org/10.1186/s13058-026-02400-x

Image Credits: AI Generated

DOI: 10.1186/s13058-026-02400-x

Keywords: breast cancer, treatment delay, time to treatment initiation, overall survival, stage III breast cancer, triple-negative breast cancer, cardiovascular comorbidity, Korean cohort, retrospective study, Cox proportional hazards, molecular subtype, K-CURE database