This examination of chemoprevention adherence in the NSABP BCPT revealed that heavy alcohol users were less likely to adhere fully in the short term, and cigarette smokers were less likely to adhere adequately in the long term, whereas obesity and physical activity were not associated with adherence. A detailed pill adherence sub-study of 100 participants in the International Breast Intervention Study (IBIS), a European study of tamoxifen for prevention of breast cancer, also reported lower adherence for women who smoked.30
In the second NSABP breast cancer prevention trial, the Study of Tamoxifen and Raloxifene (STAR; also known as P-2), women with a smoking history were less likely to persist in taking their assigned drug.31
Smoking has also been associated with poor adherence to breast cancer screening.32
For those women who do smoke and yet adhere to chemoprevention, it is unclear whether this inconsistent behavior is due to differing perceptions of personal risk of breast cancer versus diseases more commonly associated with smoking, or of the relative costs and challenges of smoking cessation versus chemoprevention adherence. It has been observed that a person's perceived risk tends to reflect underestimation or optimistic bias relative to objective risk.33
The IBIS investigators did not examine the impact of alcohol, leisure-time physical activity, or obesity, and we found no other studies examining associations between these behaviors and chemoprevention adherence. Our results regarding other medical and demographic factors confirmed associations observed in IBIS including age and risk of breast cancer. STAR, as well as several studies regarding adjuvant tamoxifen therapy and other medications, found greater persistence or adherence for older patients5,6,31,34-37
although inverse or U-shaped associations have also been observed.3,38
Veronesi reported that breast cancer patients taking tamoxifen in an adjuvant therapy trial were more likely to adhere than were women in a chemoprevention trial, which is consistent with our observation that higher perceived health risk increases adherence.39
Similarly in STAR, persistence was higher among those with higher predicted breast cancer risk.31
Although having higher income was positively associated with adherence, we found inconsistent associations with education: an inverse association in the short term, positive association in the long term. Past literature in other settings has also not consistently reported a positive association with education.40,41
Our finding that being Hispanic was associated with worse short-term adherence in our study was consistent with literature, but other studies have also reported associations with Black race as well as marital status.37,38,41
Some past studies have been observational, reflecting adherence in general clinical practice rather than in the clinical trial setting, which also might account for differences.
We considered both full and adequate adherence to be of interest because this study has implications for adherence to oral therapies in general, and in other settings higher levels of adherence may be necessary to achieve efficacy. Therefore, although 75% adherence might be the most clinically important endpoint for tamoxifen, we also provide results for full adherence.
The lack of strong associations with obesity and physical activity suggest that poor adherence is not simply based on a pattern of unhealthy behavior in general, but could be related to common sociological, psychological, biological, or genetic mechanisms that impact both substance use and medication adherence. The present report was limited to baseline factors – those factors that would enable a care provider to predict poor adherence at the start of treatment. Separately, we will report associations of adherence with the participant's experience while on treatment, including quality of life and symptoms. In that report, we will examine whether smoking and alcohol use were associated with worse symptoms and quality of life, mediating their effects on adherence. Past studies have examined how emotional factors influence decision making about tamoxifen.42,43
Differences in emotional factors and symptoms might also help explain the higher adherence among older women. Older women had lower levels of emotional distress and fewer vasomotor symptoms.28
The effectiveness of breast cancer chemoprevention for high-risk women has been demonstrated,9,44
but that benefit will only be translated to the general population if women adopt and adhere to a chemopreventive agent. While we are ultimately concerned with adherence to the 5-year regimen in clinical practice, our study examined adherence in the context of a placebo-controlled clinical trial. In clinical practice, adherence might be supported because all patients are receiving a proven therapy. However, given the active adherence promotion by BCPT headquarters and institutional clinical staff, and other factors noted in the literature, it is likely to have been higher in the BCPT.45
Our report does not address strategies to improve adherence in clinical practice, and does not provide data beyond three years, after which adherence might continue to decline. It is worth noting that in our context, even women who were of healthy weight, non-smoking, moderate alcohol users, white, older than 60, and college educated had some problems with adherence. However, the need to better define the patient groups at risk for non-adherence has been noted in the literature.40,46
Additional adherence interventions targeting women who smoke cigarettes and drink alcohol and addressing the underlying factors that lead to the unhealthy behaviors may be necessary to maximize the benefits of chemoprevention treatment.