Early discontinuation and non-adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer

Abstract

Despite the benefit of adjuvant hormonal therapy (HT) on mortality among women with breast cancer (BC), many women are non-adherent with its use. We investigated the effects of early discontinuation and non-adherence to HT on mortality in women enrolled in Kaiser Permanente of Northern California (KPNC). We identified women diagnosed with hormone-sensitive stage I-III BC, 1996-2007, and used automated pharmacy records to identify prescriptions and dates of refill. We categorized patients as having discontinued HT early if 180 days elapsed from the prior prescription. For those who continued, we categorized patients as adherent if the medication possession ratio was ≥80%. We used Cox proportional hazards models to estimate the association between discontinuation and non-adherence with all-cause mortality. Among 8,769 women who filled at least one prescription for HT, 2,761 (31%) discontinued therapy. Of those who continued HT, 1,684 (28%) were non-adherent. During a median follow-up of 4.4 years, 813 women died. Estimated survival at 10 years was 80.7% for women who continued HT versus 73.6% for those who discontinued (P < 0.001). Of those who continued, survival at 10 years was 81.7 and 77.8% in women who adhered and non-adhered, respectively (P < 0.001). Adjusting for clinical and demographic variables, both early discontinuation (HR 1.26, 95% CI 1.09-1.46) and non-adherence (HR 1.49, 95% CI 1.23-1.81), among those who continued, were independent predictors of mortality. Both early discontinuation and non-adherence to HT were common and associated with increased mortality. Interventions to improve continuation of and adherence to HT may be critical to improve BC survival.

Fig. 1

a Kaplan-Meier curve comparing continuation and discontinuation of hormonal therapy among 8,769 patients with stage I–III hormone-receptor-positive breast cancer who initiated treatment, KPNC, 1996-2007. b Kaplan-Meier curve comparing adherence and non-adherence to hormonal therapy among 5,979 patients with stage I–III hormone-receptor-positive breast cancer who continued treatment, KPNC, 1996–2007

Fig. 2

Association between degree of adherence and all-cause mortality among 5,979 patients who continued adjuvant hormonal treatment, KPNC. 1996–2007. Results based on individual multivariate analysis compared to the rest of the cohort, controlling for clinical and socio-demographic variables