In this large population-based study of women with nonmetastatic BC enrolled in KPNC, we found that approximately 30% of those who began adjuvant hormonal therapy with either tamoxifen or AIs discontinued therapy early. Furthermore, we found that, of those who continued therapy, approximately 70% were fully adherent by the end of the 4.5-year period, indicating that overall only 49% of patients were fully adherent for the entire 4.5 years. We found rates of discontinuation and nonadherence to be similar from year to year. We were surprised to find that women at the extremes of the age range (ie, those < 40 years or > 75 years) were particularly likely to be nonadherent.
Our results are consistent with other studies that have shown high discontinuation and nonadherence rates among women on adjuvant hormonal therapy; however, slight differences are seen based on the methodology used to define adherence, and the patient populations studied. Prior studies were limited to patients older than age 65 years,31,32
had smaller sample sizes,12,33
included only patients on Medicaid,12,33
were unable to censor at the time of insurance disenrollment/progression, defined discontinuation with a shorter time interval from last prescription,12,31–33
or had < 5 years of follow-up (2.5-4.5 years).14
Despite these differences, the prior studies all consistently reported discontinuation rates in the range of 30% to 50%.
Most of the population-based studies on quality of cancer chemotherapy have used the SEER-Medicare database and, as a result, have focused on patients older than age 65 years.7,34,35
Most of the studies on adherence to adjuvant hormonal therapy have also investigated patients in this older age range.13,16,31,36
Thus, less is known about younger age groups. In our study, we found that, compared with women age 50 to 65 years, younger women were more likely to discontinue therapy early and more likely to be nonadherent. Two prior studies also found younger age to be a predictor of early tamoxifen discontinuation19,33
; however, this finding has received little attention. Young adults with cancer may be a particularly vulnerable group.37–39
While this may not reflect our patient population, patients in this age group have the lowest rates of health insurance coverage, frequent delays in diagnosis, and the lowest accrual to clinical trials.38
Against this background, young adults with cancer have unique challenges—medically, psychosocially, and economically—that are now beginning to be appreciated and addressed and may result in improved treatment quality.39
Similar to other studies in the literature,40,41
our study found longer prescription refill intervals (60 or 90 days v
30 days) to be associated with both completion and full adherence to hormonal therapy. However, the link between nonadherence and length of prescription refill may simply reflect greater opportunities to detect poor adherence when more refills are required. On the other hand, shorter refill intervals may be associated with an increased frequency of nonadherence because of the inconvenience involved in frequent refilling. Further research is needed to explore the impact of prescription refill interval on medication adherence.
Much of the research on health disparities in treatment quality has focused on differences between African American and white women. For example, African American patients receive less aggressive intravenous chemotherapy,42
have fewer consultations with medical oncologists,43
and have a significantly higher risk of recurrence than whites.44
It is estimated that only 50% of African American women appropriate for adjuvant chemotherapy for BC receive it.45–47
Similar to other studies,33
after controlling for confounding factors, our study showed that African American women were more likely to be nonadherent to therapy compared with white women, but there was no difference in discontinuation rate.
Interestingly, we found that Asian/Pacific Islander women were significantly less likely than other racial/ethnic groups to discontinue therapy, but there was no difference in rates of nonadherence. In several population-based studies,48,49
Asian/Pacific Islander women were significantly more likely to undergo mastectomies than white women.50
There may be treatment differences across subpopulations of Asian/Pacific Islander women and/or treatment differences related to immigration, language, and acculturation factors that we were not able to evaluate in this study. For example, in one study based on Bay Area SEER data, Chinese women were more likely than white women to not receive adjuvant therapy.50
Barriers to adherence include failure of the physician to carefully explain benefits and adverse effects, not giving consideration to cost, and a poor therapeutic relationship.1
With regard to cancer, adherence to hormonal therapy is highly dependent on the communication between physician and patient.32
We found that 13% of patients who continued hormonal therapy were nonadherent from the first refill. It might be helpful to identify interventions to improve adherence at this time point. Treatment-associated toxicities are another major barrier to the full application of effective cancer treatment. For example, in a survey of 622 postmenopausal women, 30% discontinued AI therapy, and 84% did so because of adverse effects.51
This may partially explain our high nonadherence rate with AI therapy. We found that 4% of patients filled only one prescription for their hormonal therapy; this early discontinuation may be related to early treatment toxicities, among other factors.
Financial issues, such as lack of coverage for prescriptions, also inhibit full adherence with oral therapies. The total cost of tamoxifen may be as high as $1,200 per year52
and, before going off patent, AIs cost about $2,300 per year.53
Factors such as copayments have been shown to influence adherence. Goldman et al54
found that a doubling of copays for various chronic medications resulted in drops in adherence ranging from 8% to 45%, depending on the medication. Our study, however, was conducted in an equal-access health care system where all of the patients had a pharmacy plan, thus somewhat controlling for insurance status and copays, so that other factors could be examined.
There are several limitations to our study. First, we were unable to determine the reasons for nonadherence and discontinuation. Another limitation was the inability to capture all recurrences with electronic medical data, which may have led to misclassification bias. In addition, assumptions were made to calculate total number of pills dispensed because of the lack of prescription information (dosage and days supplied), which may have resulted in an under- or overestimation of the number of pills dispensed; however, use of prescription claims databases to estimate medication adherence has been validated in other studies.55
We found that only 49% of patients with hormone-sensitive BC continue therapy and take medications in the prescribed fashion until the end of the 4.5-year course, whether they are taking tamoxifen or AIs. Further investigation is warranted to determine the association between nonadherence to hormonal therapy and breast cancer–specific mortality. Ultimately, interventions need to be defined to help such patients comply with the full course of adjuvant hormonal therapy.