OBJECTIVES: Endocrine therapy is the mainstay of treatment for breast cancer (BC) to reduce the risk of BC recurrence. Treatment-related adverse events (e.g., musculoskeletal/joint pain) may result in treatment nonadherence or discontinuation and, thus, may increase the risk of BC recurrence. We aimed to examine the association between nonadherence to endocrine therapy and recurrence risk among BC survivors by conducting a systematic literature review.

METHODS: We conducted a systematic search of PubMed/MEDLINE for randomized controlled trials and observational studies examining associations between adherence to endocrine therapy and recurrence in BC survivors through 10/1/2020. We excluded non-English articles, case reports, reviews, meta-analyses, and editorials/commentaries.

RESULTS: We screened 453 articles and included 6 observational studies (all BC stages [n=2]; non-metastatic [n=3]; not reported [n=1]). Definitions of nonadherence in the studies varied: proportion of days covered (PDC) <80% (n=2), or PDC <90% (n=1), medication possession ratio <80% (n=1), prescription refill gaps >28 days (n=1), and cumulative prescription refill gaps >180 days (n=1). The studies’ reported outcomes included time to recurrence after BC diagnosis (n=3) or BC surgery (n=1) and recurrence within 1 (n=1) or 4 years (n=1) of endocrine therapy. Four out of five European studies found that nonadherence to endocrine therapy was associated with an increased recurrence risk (adjusted hazard ratios range=1.39-1.71), although adherence measurement periods varied within 2.7–5 years. One US study found no association between recurrence risk and nonadherence to endocrine therapy for one year after initiating treatment.

CONCLUSIONS: This systematic review suggests that long-term nonadherence to endocrine therapy is associated with an increased recurrence risk. Future observational studies are needed to investigate the impact of early nonadherence to endocrine therapy on recurrence risk, and to identify potential barriers to optimal medication adherence among BC survivors.