Adherence to endocrine therapy and survival outcomes in hormone receptor-positive breast cancer

To evaluate the association between adherence to adjuvant endocrine therapy and overall survival as well as breast cancer-specific survival in patients with hormone receptor-positive breast cancer, to characterize the dose-response and dynamic trajectory features of adherence, and to explore the potential mediating roles of treatment interruption and subsequent treatment escalation.

This single-center real-world cohort study enrolled patients with hormone receptor-positive breast cancer who underwent surgery and initiated adjuvant endocrine therapy. Adherence was assessed during the first 12 months following treatment initiation using a prespecified landmark design to mitigate time-related biases. The primary exposure, proportion of days covered, was analyzed both as a dichotomized variable for stratified comparisons and as a continuous variable for dose-response and non-linear modeling; longitudinal trajectory analysis was further applied to identify distinct long-term adherence behavioral phenotypes. The primary outcome was overall survival, and the secondary outcome was breast cancer-specific survival. Propensity score weighting was employed to balance baseline characteristics, and competing risk regression was used for cause-specific mortality. Mediation analysis was conducted to quantify the indirect effects of treatment interruption and subsequent treatment escalation in the adherence-prognosis pathway.

Over the follow-up period, high adherence was significantly associated with superior overall survival, an association that remained robust after propensity score weighting. Competing risk analysis demonstrated that high adherence was also associated with a reduced risk of breast cancer-specific mortality. Dose-response analysis revealed a non-linear relationship between adherence and mortality risk, with the steepest risk reduction observed in the moderate adherence range. Trajectory analysis identified distinct patterns of adherence-including persistently high, gradual decline, and persistently low-with the rapid-decline and persistently low trajectories conferring the highest risk of adverse outcomes. Mediation analysis indicated that treatment interruption and subsequent treatment escalation partially explained the association between adherence and survival.

In this real-world population, adherence to adjuvant endocrine therapy is closely associated with survival outcomes in hormone receptor-positive breast cancer, exhibiting dose-response and dynamic trajectory characteristics. Conceptualizing adherence as a continuous, time-varying behavioral phenotype may enable more precise identification of at-risk populations and inform optimization of long-term management strategies.