Impact of early discontinuation of adjuvant endocrine therapy on survival in breast cancer: A target trial emulation

Abstract

Background: Early discontinuation of adjuvant endocrine therapy (AET) among patients with estrogen receptor-positive (ER+) breast cancer (BC) is common. Observational studies reported inconsistent effects of early AET discontinuation on survival outcomes, with limited causal evidence.

Methods: We identified women aged 50-80, diagnosed with first primary ER+ BC between 2010-2015, who underwent surgery in Alberta, Canada. The average effect of early AET discontinuation on survival outcomes was estimated by emulating a target trial. Risk factors for early AET discontinuation were evaluated.

Results: Of 6823 eligible patients, 21.8 % did not receive AET, 27.3 % discontinued AET within early, and 50.9 % adhered to the 5-year AET. Compared to adhering to 5-year AET, early discontinuation increased the hazard of overall death and recurrence, with greater effects in higher tumor stages. Early discontinuation also significantly increased the risk of breast cancer-specific death (HR=3.92, 95 % CI: 2.96-5.20), but no interaction with tumor stage was observed. No significant difference in survival outcomes was observed between patients discontinuing AET at 4-5 years and those completing 5 years. Older age (>70 years) at diagnosis, lower-stage disease, HER2-negative status, and absence of chemotherapy or radiotherapy were associated with early discontinuation.

Conclusions: Over one-third of ER+ BC patients in our cohort discontinued AET early, which was associated with increased risks of recurrence and mortality. The impact of early discontinuation varied by tumor stage, and one-year reduction in AET duration did not appear to compromise effectiveness. Implementing targeted interventions for ER+ patients may help improve adherence and survival outcomes.

Keywords: Adjuvant endocrine therapy; Breast cancer; Early discontinuation; Target trial emulation; Treatment effects.