Hormone Therapy Adherence and Costs in Women With Breast Cancer

Breast cancer is common among women in the United States, with 202,964 women diagnosed and 40,598 dying in 2007.¹ National cancer care expenditures have steadily increased in the United States and were the largest for female breast cancer, with $13.9 billion in 2006 and nearly 45% of the expenditures for initial care.² Thus,treatment of breast cancer is a significant economic burden to patients, their families, and society as a whole.

Hormone therapy (tamoxifen and aromatase inhibitors [AIs]) has become an integral part of treatment among women with hormone receptor—positive breast cancer.³ Evidence indicates that completing 5 years of hormone therapy with tamoxifen or AIs has been shown to reduce disease recurrence and mortality, and hormone therapy is the recommended care for women with early-stage breast cancer.^4-8 Despite the life-threatening disease, long-term use of hormonetherapy in women with breast cancer was suboptimal, with overall more than 30% of women discontinuing the treatment in clinical settings.^9-12

The associations between medication nonadherence and risk for worsened clinical and economic outcomes in chronic diseases and depression have been shown in previous studies.^13-18 Improving medication adherence has been a promising strategy to achieve desirable health outcomes and control healthcare costs. For example, the study by Balkrishnan and colleagues¹³ found that every 10% increase in adherence was associated with a 9% to 29% decrease in annual total healthcare costs in elderly patients with type 2 diabetes enrolled in a Medicare health maintenance organization. Another study reported that adherence to antidepressants was associated with lower medical costs in patients covered by private health insurance.¹⁶ However, it is not clear whether consistent results could be observed in patients receiving hormone therapy to treat breast cancer. Long-term users ofhormone therapy could experience an increase in serious adverse events that may increase treatment costs.^19-22 Conversely, discontinuation of hormone therapy increases risk for disease progression, which may also increase costs to treat recurrent breast cancer.²³ To our knowledge, studies on the association between adherence to hormone therapy and healthcare costs are very limited. Understanding how adherence to long-term hormone therapy affects healthcare costs would help policy makers develop effective interventions to improve health and economic outcomes in breast cancer care.

We analyzed a linked data set of South Carolina Central Cancer Registry (SCCCR) and South Carolina Medicaid claims data, and performed repeated measures to assess long-term use of hormone therapy and yearly healthcare service utilization and costs across 4 years. The objective of this study was to examine the association between hormone therapy adherence and medical and total healthcare costs in low-income, insured women with breast cancer.

METHODSStudy Population

We used SCCCR and South Carolina Medicaid administrative data to conduct a retrospective cohort study coveringthe period of 2000 to 2008 among women who were enrolled in South Carolina Medicaid and initiated hormone therapy within 1 year after diagnosis of nonmetastatic and hormone receptor—positive or unknown breast cancer. Patients with dual eligibility for Medicare and Medicaid were excluded from the study. All eligible patients were continuously enrolled in Medicaid for 1 year before and at least 1 year after the index date (date of first prescription of hormone therapy) and followed up for 1, 2, 3, or 4 years. Tamoxifen and AI use was identified by national drug codes from Medicaid pharmacy claims. We restricted our analysis to women who used tamoxifen or AIs only during the study period. The de-identified SCCCR-Medicaid linked data set was provided by South Carolina Offi ce of Research and Statistics using probabilistic match. Patient fi rst name, last name,social security number, and date of birth were used for the linkage, and all personal identifiers were removed prior to data analysis. Institutional review board approval was obtained from the University of South Carolina for this research.

Measures

Proportion of days covered (PDC) was measured as a medication adherence rate, where the total number of days of supply from each filled prescription was used to calculate the proportion of days on which a patient had tamoxifen or AIs available in each interval (year 1 through year 4). The total number of patients for adherence rate measures in each interval (year 1, year 2, year 3, and year 4) varied due to variation in enrollment eligibility. Patients with partial enrollment in the given intervals were not included for adherence measures for the corresponding intervals. Thus, each subject could have at least 1 and up to 4 adherence rates for the given intervals. Thecohort was then divided into 2 groups at each interval: adherent individuals were defined as those with a PDC of at least 80% in a given interval; those with a PDC less than 80% were considered as nonadherence.^24,25

We used the amount paid by Medicaid for all healthcare services in calculation of the costs for each patient. Medical costs including inpatient, outpatient, emergency department, and physician office costs in each year were retrieved from medical claims. Pharmacy costs of all prescription drugs used each year were obtained from pharmacy claims. Annual total healthcare costs were a sum of medical and pharmacy costs associated with any conditions. Hormone therapy cost in each year was a sum of tamoxifen or AI costs. All costs were standardized to 2011 dollars for analyses. Medical utilization per year was identified from medical claims, including total numbers of physician office visits and hospital outpatient visits, and frequencies of at least 1 emergency department visit and inpatient service.

Stage categories from Surveillance Epidemiology and End Results were used to define breast cancer as localized or regional. Charlson Comorbidity Index scores based on assigned weights for a number of major conditions (ranging from 1 to 6) were calculated to reflect the severity of comorbidity.²⁶

Data Analysis

The mean PDC and percentage of patients who were adherent to hormone therapy were calculated for each year (year 1 to year 4). generalized linear models (log link and gamma distribution) with repeated measures were used to assess differences in annual total healthcare costs and medical costs between adherent and nonadherent groups after adjusting for age, race, comorbidity, cancer stage, and type of hormone therapy. The level of statistical signifi cance was set at P = .05 for all the analyses. All data were analyzed with SAS 9.2 (SAS Institute, Cary, North Carolina).

RESULTS

The final study sample consisted of 410 women who were diagnosed with nonmetastatic and hormone receptor—positive or unknown breast cancer between 2000 and 2008 and who received AIs or tamoxifen only as hormone therapy during the study period. Among the study population, 55% of patients (n = 224) initiated AIs and 45% (n = 186) initiated tamoxifen to treat breast cancer (Table 1). Black (40%) and white (47%) women accounted for a large proportion of the population. Fewer than 50% of women were diagnosed with breast cancer before 2004. Nearly half of the women in the study were diagnosed with local stage and 40% with regional stage breast cancer.

Table 2

displays the adherence rates (PDCs) for hormone therapy, medical utilization, and healthcare costs across 4 years. Mean PDCs per year ranged from 0.71 to 0.75, and more than 50% women were adherent to hormone therapy (PDC >0.8) each year during the 4-year period. Mean total healthcare costs per year ranged from $7993 to $12,373 per patient across 4 years. Pharmacy costs per year accounted for 45% to 60% of total healthcare costs across 4 years.

Table 3

displays unadjusted annual total healthcare costs, medical costs, and pharmacy costs in adherent and nonadherent women across 4 years. In general, medical costs in the adherent group appeared to be lower than those in the nonadherent group during the 4-year period. However, a similar trend was not observed in yearly total healthcare costs during the study period.

Results of regression analyses of the association between adherence to hormone therapy and total or medical costs are summarized in

Table 4

. After controlling for age, race, comorbidity, cancer stage, and type of hormone therapy, the log coeffi cient of adherence to hormone therapy in the regression model can be translated into a 31% decrease in medical costs per year across 4 years in the adherent group. No signifi cant difference in total healthcare costs was observed between adherent and nonadherent women. The Figure shows the differences in mean medical costs per year between the groups adherent and nonadherent to hormone therapy across 4 years, after adjusting for confounders. A significant reduction in medical costs for adherent patients was found in the first 2 years, though the gap narrowed in the next 2 years.

DISCUSSION

To our knowledge, this is one of the first studies to examine the relationship between medication adherence and healthcare costs in breast cancer care. In this study, we analyzed Medicaid claims data linked with cancer central registry data to explore the association between long-term use of hormone therapy and resource utilization in lowincome, insured women with breast cancer. Our study found that suboptimal adherence to hormone therapy was associated with higher medicalcosts across the 4-year period. This result is consistent with previous studies on chronic diseases such as diabetes, hyperlipidemia, and hypertension.^13-15 Sokol and colleagues¹⁴ observed lower all-cause medical costs with high levels of medication adherence (80%-100%) in patients with diabetes, hypertension, and hypercholesterolemia covered by employer-sponsored health insurance plans. Another study also reported that adherence to statin therapy was associated with a 15% decrease in medical costs in Medicaid enrollees with type 2 diabetes.¹⁵ Because patients with continuous use of hormone therapy for 5 years have a lower risk for disease progression including recurrence of breast cancer and mortality, use of high-cost health services to treat more advanced breast cancer could be reduced in the adherent group. It is worth noting that medical costs in our study varied across 4 years between the adherent and nonadherent groups. Compared with nonadherent women, adherent women had significantly lower medical costs in the first and second years of follow-up, with the gap gradually narrowing in the third and fourth years. Clinical studies indicated that the incidence of early recurrent breast cancer peaks at approximately 2 years postsurgery, and most of the early recurrence events are distant metastatic breast cancer.^27,28 Therefore, conducting early interventions to enhance continuous use of hormone therapy would be a potential strategy to reduce risk for breast cancer recurrence and to control medical costs for treating disease progression.

Unlike pharmacotherapy for diabetes, hypertension, and hypercholesterolemia, hormone therapy to treat breast cancer did not result in total healthcare cost savings for adherent women during the 4-year period. Studies on the aforementioned “lifestyle” chronic diseases concluded that in patients adherent to medications, the higher pharmacy costs might be more than offset by medical cost reductions due to lower risks for medical utilization to treat diabetic complications and coronary heart diseases, producing a net reduction in total healthcare costs. However, breast cancer management costs are composed of costs for remaining on adjuvant treatment and the costs for treating adverse events. Long-term use of hormone therapy could increase the probability of experiencing either minor or serious adverse events. If patients remained on the original hormone therapy after occurrence of adverse events, costs to manage various adverse events would be added to total healthcare costs. Further studies are needed to assess the association between longterm adherence to hormone therapy and adverse event—related costs.

It is worth noting that there was a racial difference in total healthcare costs between African Americans and Caucasians. The results in Table 4 showed that African American women had 25% lower total costs than Caucasian women after adjusting for other confounders, which warrants further studies to address the racial disparity and examine potential factors related to care management received, service area, and clinical practice in breast cancer care.

Limitations

This study was an initial exploration of the effects of adherence to hormone therapy on healthcare costs in women with breast cancer. Although claims data have been an important source to assess cost of healthcare and health service utilization for various cohorts, these data are collected for administrative purposes and several limitations should be considered. First, we included only women enrolled in Medicaid continuously for 1, 2, 3, or 4 years. It is not clear whether cost convergence in years 3 and 4 is an artifact of care continuity interacting with or mitigating the impact of adherence. Thus, sustained eligibility during the study period mandated by our selection criteria may have progressively mitigated the impact of adherence on medical costs. Second, we used prescription fill records from pharmacy claims to measure PDC as an adherence rate for use of hormone therapy. This adherence metric may not reflect whether patients truly consumed their medications or complied with dosing regimens. The assumption that a prescription fi lled is a prescription taken was made in our study. In addition, the accuracy of resource utilization and completeness of claim submissions by healthcare providers should be considered. The amount paid by Medicaid could vary due to miscoding and missing information. Finally, the study estimated medication adherence and associated healthcare costs based on South Carolina claims data. The results may not be generalized to other populations and other states as there are differences in eligibility, scope of services provided, and other policies across states.

CONCLUSIONS

This study demonstrated that adherence to hormone therapy by Medicaid beneficiaries with breast cancer across a 4-year period was associated with decreased medical costs. The greatest reduction of medical costs occurred in the fi rst 2 years after initiation of hormone therapy. The study highlights the importance of identifying women with breast cancer who are at risk for lower levels of adherence to hormone therapy and, in turn, higher medical costs owing to disease progression. Early adherence-enhancing interventions might help improve the use of hormone therapy and reduce the risk for disease recurrence. In addition, analysis of patient behaviors regarding medication use may be a potential strategy to cost-effectively manage breast cancer care in women receiving hormone therapy in practice settings. Further research is needed in larger populations to fully explore the relationship among adherence to hormone therapy, costs for treating adverse events, and recurrent breast cancer.