In this population-based study of low-income, continuously insured patients with breast cancer, we report low fill, adherence, and persistence rates to adjuvant hormonal therapy. Only 64% of women who were eligible filled any prescription for tamoxifen or an aromatase inhibitor within 12 months after diagnosis. In the year after first prescription fill, adherence (MPR > 80%) and persistence rates were 60% and 80%, respectively.
Predictors of a greater likelihood of filling a prescription for hormonal therapy were older age, more prescription medications, not being married, higher stage, having hormone receptor status of positive (v
unknown), not receiving adjuvant chemotherapy, receiving adjuvant radiation, and receiving diagnosis in a small hospital. Except in the oldest old (85 to 92 years old), for which use of hormonal therapy has been reported lower,44
other studies also found greater use with older age.12,45
With regard to ER status, lower fills with ER unknown status may reflect appropriate prescribing, but this cannot be ascertained from registry/claims data. Finally, the inverse association of adjuvant hormonal therapy and chemotherapy is similar to that of prior reports.12
We suspect that hormonal therapy is substituted for chemotherapy in cases where there is concern about toxicity. Adherence to adjuvant hormonal therapy, in these cases, would be particularly important.
Poor adherence to tamoxifen has been linked to increased risk of death from breast cancer.18
In their retrospective cohort study of 2,080 patients with breast cancer, Thompson et al18
reported tamoxifen prescription rate of 79%, median adherence of 93% (interquartile range, 84% to 100%), and reduced breast cancer survival with lower adherence. Furthermore, Thompson and other investigators reported that longer duration of tamoxifen use was associated with improved survival.1,28
In this low-income, insured population, the adherence rate (defined as MPR > 80%) of only 60% within the first year of adjuvant hormonal therapy is lower than rates reported in other studies.14,16,17
Among women initiating tamoxifen for primary breast cancer and who were enrolled in New Jersey Medicaid or Pharmaceutical Assistance to the Aged and Disabled programs, nonadherence (defined as ≤ 80% of eligible days covered by prescription tamoxifen) within the first year after prescription was only 17%.16
When interviewed, only 8% of women ≥ 65 years of age with hormone receptor–positive breast cancer from four regions in the United States reported nonadherence to tamoxifen within the first year after prescription.14
In a study of three large commercial health programs, the nonadherence rate (defined as MPR < .80) to anastrozole within 12 months of prescription ranged from 12% to 18% among the health plans.17
We suspect that the high nonadherence rate of 40% in our study, despite continuous insurance coverage that included prescriptions at a low copay rate, was related to the population—a uniformly low-income population in NC.
The nonpersistence rate of 20% within 1 year after initial prescription is also higher than that of most previous reports and is worrisome because it is likely that persistence to adjuvant hormonal therapy declines further over subsequent years of treatment. Rates of discontinuation, or nonpersistence, reported in clinical trials of adjuvant tamoxifen range from 16% to 32% at 5 years.46–50
Persistence rates for patients not participating in clinical trials are typically lower.10,12,14
These studies, however, primarily focused on older patients and used patient self-report as a measure of treatment discontinuation, a method that has considerable limitations and may significantly underestimate the true rate of nonpersistence.13,51
There are two reports of persistence to tamoxifen therapy based on prescription fills. The first is a study of women ≥ 65 years of age in six health care delivery systems in the United States describing discontinuation rates (defined as no tamoxifen for 60 days) of 15%, 24%, 33%, 40%, and 49% at 1, 2, 3, 4, and 5 years, respectively.15
The second was a study of the Irish Health Service Executive Primary Care Reimbursement Services pharmacy database and reported a discontinuation rate at 1 year similar to that seen in our study (22%), but with a significantly more stringent definition of nonadherence (180 consecutive days with no tamoxifen or alternative hormonal therapy); at 3.5 years, 35% had discontinued.52
Even in the Irish system of “equal” access, therefore, many women did not continue therapy through the full course. We project that the low rate of persistence to adjuvant hormonal therapy at 1 year among these low-income women only leads to lower rates in subsequent years and may contribute to the poor outcomes seen in this population.
In multivariate analyses, we found that not being married was positively associated with adherence and persistence. Higher comorbidity and stage were predictive of persistence but not of adherence. Age, race, and tumor management were not significantly associated with adherence or persistence. We are not aware of other studies reporting a relationship between marital status and adherence or persistence with adjuvant hormonal therapy for breast cancer. Conversely, in other chronic diseases, social support and being married were associated with greater medication adherence.53
We lack a good explanation for this finding, but suspect that it reflects a different pattern of social support in this particular population.
There are three general strengths of this study. First, this database of Medicaid-insured women provides a uniformly low-income population for study. Second, linking Medicaid and NC CCR data allows accurate stage designation, which is otherwise not available from Medicaid claims alone. Third, Medicaid has a prescription plan, allowing for accurate tracking of prescription fills. As opposed to other databases, such as Surveillance, Epidemiology, and End Results, where prescription information is not available and reporting of hormonal therapy is limited by the ability of registrars to collect the information (κ of 0.52 for registry v
medical chart review),54
we are able to directly measure prescription fills. Of note, we included only women who were continuously covered by Medicaid insurance for 24 months, either as Medicaid only or as dually insured by Medicaid and Medicare, and thus provided information across age groups. Furthermore, with information about all filled prescriptions in the Medicaid database, we captured patients who switched to other, alternative, acceptable hormonal agents and included them as adherent or persistent, therefore presenting potentially more comprehensive information than has previously been possible.
We recognize that there are limitations to the study. First, we lack information about individual patient adverse effects or health literacy, which are known to be linked to treatment adherence and persistence.9,10
Second, in this administrative data set, we cannot determine whether a prescription is not written, as well might be the case for women enrolled in Medicaid,55
or whether it was written and not filled. Alternatively, medication provided as samples or through patient assistance programs is not captured, though use of patient assistance programs was unlikely, because there is nominal cost to prescriptions with Medicaid. Finally, we dichotomized medication adherence and persistence behaviors in our multivariate analyses, which may have limited our ability to find significant associations among variables. Sensitivity analyses were conducted using multivariate models treating these variables as continuous and time series, respectively, and we did not find any differences in the direction and significance of the estimates.
In summary, use of adjuvant hormonal therapy, as measured by prescription fill adherence and persistence, was low in this group of low-income, insured women who were eligible for adjuvant hormonal therapy for breast cancer. Given its impressive therapeutic efficacy1
and low toxicity relative to adjuvant chemotherapy, consensus guidelines56–58
recommend that adjuvant hormonal therapy be offered to women with hormone receptor–positive breast cancer. We propose that improving use of adjuvant hormonal therapy will improve breast cancer outcome in low-income and underserved populations. The next steps for this research will be to find modifiable risk factors for low use of adjuvant hormonal therapy in this low-income population and to design interventions. This will likely require study outside claims data. Factors such as care processes, patient-physician communication, reduced adherence owing to side effects, and patient knowledge or beliefs regarding treatment are not available in administrative data and will need to be explored. Whatever the method, a successful approach to this problem will likely lead to improved care for underserved patients in other areas as well.