Nonadherence to Adjuvant Hormonal Therapies in Breast Cancer
Chlebowski and Geller reviewed the literature on adherence to endocrine therapy in 2006 and found nine papers on breast cancer. This article seeks to review the empirical literature since that time, to see whether adherence rates have changed with additional experience using these agents, and to explore papers that examine adherence in AIs, which have come into widespread use more recently. As such, we focused on papers published after 2006 that assessed adherence to SERMs or AIs for breast cancer adjuvant treatment in the context of clinical practice (rather than in clinical trials). We limited our review of adherence rates to publications with a sample size of at least 100.
Table 1 presents a summary of findings on adherence to tamoxifen,[11,15–19] and Table 2 on adherence to AIs and/or tamoxifen, including women who may have used both tamoxifen and one or more AIs[20–27] (interestingly, no studies to date have yet reported adherence to the SERM raloxifene, a US FDA-approved agent for breast cancer risk reduction). Readers are invited to consult the full studies for additional details and findings. We used the WHO's definition of adherence, which is: "the extent to which a person's behaviour – taking medication, following a diet, and/or executing lifestyle changes, corresponds with agreed recommendations from a healthcare provider". This definition of adherence includes intermittent use, less-than-prescribed dosages and premature discontinuation all as constituting nonadherence. Given the rather small amount of literature in this area, we felt that a broad definition was warranted; some studies have distinguished between different types of adherence, such as never filling one's prescription, or levels of intermittent adherence (e.g., [18,25]).
We identified 14 studies, five of which have been published in 2011. This is clearly an area of considerable current interest. The studies vary considerably in their patient populations, the way that adherence is measured, the sources of data, the duration of adherence that is observed, as well as the findings. However, despite these differences, it is clear that nonadherence is a concern in all studies. Not surprisingly, adherence is better at 1 year, with rates of adherence in studies that reported 1 year adherence ranging from 77 to 88%,[20,23,25,26] whereas studies reporting 4–5-year prescription-based adherence found rates between 27 and 49%.[21,23] It should be noted that these figures are very similar to those reported previously for clinical practice settings, in which 30–50% of patients were nonadherent by 4 years. Studies that used patient self-reports of adherence yielded higher rates;[17,27] Ziller et al. found that whereas all 100 women in their study said that they adhered to their tamoxifen or AI regimen, prescription database information showed that actual adherence was likely to be 20–30% less.
Correlates of adherence vary, in many cases determined by the variables available in the dataset used. Age is frequently found to correlate with adherence, with nonadherence found to be higher in older[17,19–21,23,24] and younger[18,20–22,26] cohorts; given that not all studies included the same age ranges, these data are inconclusive at present, although it appears that middle-aged women (e.g., aged 50–69 years) may be most adherent. Low social support was associated with lower adherence in several studies,[16,17] but being married was linked with both lower adherence and higher adherence. Side effects were cited in two studies,[16,17] as was greater comorbidity.[19,21,26] Studies that reported both tamoxifen and AI adherence consistently reported better adherence with AIs,[20,22,27] although the women who received these different treatments differed in other important ways, such as age.
Expert Rev Pharmacoeconomics Outcomes Res. 2011;11(6):709-715. © 2011 Expert Reviews Ltd.