Factors associated with compliance to adjuvant hormone therapy in Black and White women with breast cancer

An estimated 75% of breast cancers express estrogen and/or progesterone receptors. For women with these cancers, treatment with five years of adjuvant hormone therapy (AHT), either tamoxifen or an aromatase inhibitor, has been shown to decrease the risk of both breast cancer recurrence and mortality by about a third throughout the first 15 years (Davies et al. 2011). Recent data has shown that continuation of tamoxifen in women with ER + disease for 10 years produces a further reduction in recurrence and can approximately halve breast cancer mortality during the second decade after diagnosis (Davies et al. 2013; Gray et al. 2013). Despite these benefits, studies have demonstrated adherence rates to range from 41% to 72% and non-persistence (discontinuation of therapy before completion of 5 years) to range from 31% to 73%.

Previous studies have identified multiple risk factors for therapy noncompliance including extremes of age (Barron et al. 2007), concomitant antidepressant use (Demissie et al. 2001), lack of social support (Kahn et al. 2007), and side effects experienced (Lash et al. 2006; Murphy et al. 2012). Ethnic and racial variations in medication compliance have also been demonstrated. A number of studies show lower rates of compliance and an increase in mortality among ethnic minorities, particularly Black women (Patridge 2003; Kim et al. 2008; Hershman et al. 2011; Hershman et al. 2009). Studies aimed at improving compliance rates have largely focused on reducing the negative side effects of therapy, however; a number of women do not experience adverse effects and are still noncompliant. Identifying modifiable factors contributing to therapy noncompliance may have significant benefits in improving breast cancer survival.

Models from health psychology have been applied to studies of medication compliance (Kucukarslan 2012). Social cognition models such as the health belief model assumes that individuals develop beliefs that influence the interpretation of information and guide behavior (Horne & Weinman 1999). A number of studies have investigated the impact of perceived benefit of AHT on compliance rates (Barron et al. 2007; Lash et al. 2006; Grunfeld et al. 2005; Fink et al. 2004; Cluze et al. 2012; Kirk & Hudis 2008; Pellegrini et al. 2010; Thewes et al. 2005; Kimmick et al. 2009; Shelton et al. 2013). Grunfeld and colleagues found that adherers were more likely to report a belief in tamoxifen benefit whereas non-adherers were more likely to report no benefit (Grunfeld et al. 2005). In a follow-up study conducted two years after initiation of therapy, Fink and colleagues found that patients’ perceived risk versus benefit of tamoxifen was critical to sustaining adherence after the immediate threat of a breast cancer diagnosis had passed (Fink et al. 2004). Other studies demonstrate a correlation between perceived benefit and future compliance. In a follow-up study of elderly women conducted 5-years after initiation of therapy, Lash and colleagues found that the perceived benefit of therapy assessed at baseline corresponded to future compliance (Lash et al. 2006).

Few studies have examined the association of race with attitudes regarding adjuvant hormone therapy. Shelton and colleagues found significant differences in provider communication, patient involvement in decision making, and medical trust by race of patients (Shelton et al. 2013). However, to the best of our knowledge, no study has specifically assessed whether or not differences in perceived benefit of AHT exists between Black and White women and how this impacts overall compliance rates.

Our study sought to examine factors associated with compliance to AHT in Black and White women with ER + breast cancer at a tertiary urban medical center.

This research was approved by the University of Chicago institutional review board and patients provided written informed consent for survey participation and retrospective data analysis.

We found that for both Black and White women, perceived importance of AHT in reducing their risk for developing recurrent breast cancer and the degree to which they valued their doctor’s opinion were the most important factors contributing to their overall compliance to therapy. Interestingly, education, income, concerns surrounding medication side effects, and out of pocket expenses did not appear to significantly impact reported rates of either therapy adherence or overall compliance in our cohort. Thus perception of the importance of AHT and enhanced doctor-patient communication may be important modifiable factors that can improve compliance to AHT.

In our study, patients who significantly valued their doctor’s opinions in general were more compliant to therapy. The doctor-patient relationship (Stavropoulou 2011) and doctor-patient communication (Bultman & Svarstad 2000) has been studied extensively in the adherence literature. Studies examining barriers to statin compliance have found communication patterns between patients and their clinical providers influence statin-adherence behaviors (McGinnis et al. 2007) and medical outcomes (Molfenter et al. 2012; Kaplan et al. 1989). Although a recent randomized prospective study examining the influence of educational materials on adherence to aromatase inhibitors found no difference in compliance and persistence between groups that received the educational materials versus those that did not, it is likely that educational materials alone may not be sufficient and a multidisciplinary approach is required (Yu et al. 2012). Further supporting this is a study by Shelton and colleagues which examines doctor-patient communication in patients receiving adjuvant therapy (including chemotherapy) for breast cancer. They found that enhanced provider contact increased compliance rates (Shelton et al. 2013). Thus doctor-patient communication beyond the distribution of educational materials is one possible modifiable mechanism to improve compliance.

One strength of our study is our ability to link chart review with survey responses. We were able to correlate patients’ perceived benefit of AHT and reported adherence rates with eventual completion of AHT as documented by medical records in a cohort study design, which enhances causal inference.

A limitation of our study is the use of a self-reported adherence by survey participants. We recognize that women who participate in surveys differ from those who do not (Font et al. 2012). Although our study results suggest that Black and White survey participants who perceive AHT as important are also more likely to be both adherent and compliant to therapy, it is unclear if this observation holds for nonparticipants.

Contrary to other studies examining compliance to therapy, we found no significant difference in reported adherence or overall compliance rates between Black and White women. Several explanations are possible. Although Black women in our study had lower education levels, lower income levels, and more chronic health conditions, Black women had better insurance coverage for medications compared to White women. Thus Black women who participated in our survey had greater access to medications than White women. Another possible explanation is that our study may have been underpowered. Although we had enough power to detect a greater than 15% difference in compliance rates it is possible that true compliance rates differ by less than 15%.

Given the increase in the number of oral anti-cancer medications, identifying modifiable barriers to the use of oral therapy, especially in minority women, is critical to improving survival. Prospective studies examining factors associated with non-initiation, non-adherence, and early discontinuation of adjuvant hormone therapy are underway with special attention to ethnic minorities (Neugut et al. 2012). Perceived therapy importance and doctor-patient communication on medication compliance represent modifiable variables which can improve overall cancer survival. Further prospective studies are needed to validate these findings.