Adherence to adjuvant endocrine therapy including GnRH-analogues and survival: a population-based cohort study

Adjuvant endocrine therapy (AET) combining gonadotropin-releasing hormone analogues (GnRHa) with tamoxifen (TAM) or aromatase inhibitors (AI) improves survival in premenopausal women with breast cancer compared to TAM and is increasingly prescribed. However, there are concerns regarding adherence.

Through linkages to Swedish national healthcare registers, we conducted a population-based cohort study including women diagnosed with early, invasive, estrogen receptor-positive breast cancer, January 2007 to December 2020, in the Stockholm-Gotland region, Sweden, with at least one dispensation of oral AET (n = 16,468). Follow-up ended January 14, 2022.AET was categorized based on the first dispensed oral AET (AI or TAM) and if GnRHa had been dispensed within three months of this, into the respective combination group (GnRHa + TAM or GnRHa + AI). Adherence was defined as a medication possession ratio ≥80% over five years for oral AET and two years for GnRHa, or the shortest interval from first dispensation to recurrence, contralateral breast cancer, death, emigration, or end of follow-up, if they preceded five and two years, respectively.To study the association of type of AET and non-adherence, odds ratios (OR) were calculated using logistic regression. The association between non-adherence and invasive breast cancer-free survival (IBCFS) was studied with landmark analysis, calculating hazard ratios (HR) using the Cox proportional hazards model and flexible parametric modeling.

Adherence was 86% to AI, 79% to TAM, 75% to both TAM + GnRHa, and AI + GnRHa (p < 0.001). Adjusted OR for non-adherence was 1.40 (95% confidence interval (CI) 1.27-1.55) for TAM, 2.73 (95% CI 2.19-3.40) for TAM + GnRHa, and 2.92 (95% CI 2.24-3.79) for AI + GnRHa, respectively, compared to AI. Adjusted HR of IBCFS were 1.43 (95% CI 1.26-1.64) and 1.19 (95% CI 1.04-1.35) at one- and five-year landmark analysis, respectively, comparing non-adherent to adherent groups.

Adherence was lower to combination regimens than to single AET, and non-adherence was associated with poorer survival. Future prospective studies are warranted to validate these findings.

This work was supported by grants to TF from the Swedish Cancer Society (Cancerfonden) (grant no. 21 1800Pj), Vetenskapsrådet (grant no. 2021-03061), Cancerföreningen i Stockholm (grant no. 234073), and Region Stockholm (Stockholms Läns Landsting) (grant no. FoUI-974936).