The Association Between Trajectories of Adherence to Endocrine Therapy and the Risk of Breast Cancer Recurrence Among Nonmetastatic Breast Cancer Survivors

Background: Endocrine therapy is the mainstay treatment for nonmetastatic breast cancer (BC) to reduce BC recurrence risk. During the first-year of endocrine therapy use, nearly 30% BC survivors were nonadherent, which may increase the risk of BC recurrence. Little is known about the patterns of adherence to endocrine therapy that are most associated with BC recurrence risk among BC survivors.

Objectives: To examine the association between trajectories of endocrine therapy adherence and the risk of BC recurrence among nonmetastatic BC survivors.

Methods: A retrospective cohort study included female Medicare beneficiaries with incident nonmetastatic BC who initiated endocrine therapy using the 2010—2019 Surveillance, Epidemiology and End Results (SEER) linked Medicare data. We calculated monthly fill-based proportion of days covered (PDC) in the initial 12 months of endocrine therapy and applied group-based trajectory models to identity distinct adherence patterns of endocrine therapy. We estimated the risk of recurrent BC after endocrine therapy initiation for each trajectory using inverse-probability-of-treatment-weighted Cox proportional hazards models. All analyses were stratified by cancer stages (stage 0-I and stage II-III).

Results: For stage 0-I BC survivors (n=28,188, mean age=72.3, White=85.7%, and having BC recurrence=1.5%) and stage II-III BC survivors (n=8,461, mean age=71.6, White=82.7%, and having BC recurrence=15.5%), we identified 5 distinct adherence trajectories of endocrine therapy. Among stage 0-I BC survivors, compared to women with nearly perfect adherence (51.1% of the cohort), those discontinuing before 6 months (adjusted hazard [aHR]=1.74, 95%CI=1.40-2.16) and those refilling intermittently (aHR=1.41, 95% CI=1.11-1.80) were associated with increased BC recurrence risks. Among stage II-III survivors, compared to women with nearly perfect adherence (58.0%), there was a decreased risk of BC recurrence among those who refilled intermittently (aHR=0.78, 95%CI=0.63-0.96).

Conclusions: Among female Medicare nonmetastatic BC survivors, adherence patterns of endocrine therapy varied within the first year of treatment initiation. Stage 0-I BC survivors who discontinued endocrine therapy before 6 months of the treatment or intermittently refilled endocrine therapy prescriptions were associated with increased recurrent BC risks, and may benefit from targeted interventions (e.g., medication therapy management follow-up). Future studies are needed to investigate and validate our findings on a decreased risk of BC recurrence among stage II-III BC survivors refilling endocrine therapy intermittently.