Early Discontinuation and Nonadherence to Adjuvant Hormonal Therapy in a Cohort of 8,769 Early-Stage Breast Cancer Patients

Abstract

A B S T R A C T PurposeWhile studies have found that adjuvant hormonal therapy for hormone-sensitive breast cancer (BC) dramatically reduces recurrence and mortality, adherence to medications is suboptimal. We investigated the rates and predictors of early discontinuation and nonadherence to hormonal therapy in patients enrolled in Kaiser Permanente of Northern California health system. Patients and MethodsWe identified women diagnosed with hormone-sensitive stage I-III BC from 1996 to 2007 and used automated pharmacy records to identify hormonal therapy prescriptions and dates of refill. We used Cox proportional hazards regression models to analyze factors associated with early discontinuation and nonadherence (medication possession ratio Ͻ 80%) of hormonal therapy. ResultsWe identified 8,769 patients with BC who met our eligibility criteria and who filled at least one prescription for tamoxifen (43%), aromatase inhibitors (26%), or both (30%) within 1 year of diagnosis. Younger or older age, lumpectomy (v mastectomy), and comorbidities were associated with earlier discontinuation, while Asian race, being married, earlier year at diagnosis, receipt of chemotherapy or radiotherapy, and longer prescription refill interval were associated with completion of 4.5 years of therapy. Of those who continued therapy, similar factors were associated with full adherence. Women age younger than 40 years had the highest risk of discontinuation (hazard ratio, 1.51; 95% CI, 1.23 to 1.85). By 4.5 years, 32% discontinued therapy, and of those who continued, 72% were fully adherent. ConclusionOnly 49% of patients with BC took adjuvant hormonal therapy for the full duration at the optimal schedule. Younger women are at high risk of nonadherence. Interventions to improve adherence and continuation of hormonal therapy are needed, especially for younger women.

Predicting Adherence to Tamoxifen for Breast Cancer Adjuvant Therapy and Prevention

“…Previous reports have shown that approximately 1 in 5 adjuvant tamoxifen users fail to achieve an optimal adherence threshold of 80% or greater during the first year of treatment, and there is a 7% to 10% discontinuation rate per year (12,14,15). By year 4 or 5 of treatment, the full adherence rate drops to 50% (14,16). Similarly, nonpersistence with adjuvant tamoxifen is about 20% to 30% at year 1 or 2 (15,17,18) and climbs to as high as 49% before the completion of 5 years (15,16,19).…”

“…By year 4 or 5 of treatment, the full adherence rate drops to 50% (14,16). Similarly, nonpersistence with adjuvant tamoxifen is about 20% to 30% at year 1 or 2 (15,17,18) and climbs to as high as 49% before the completion of 5 years (15,16,19). Available data on the association between adherence to adjuvant tamoxifen therapy and breast cancer outcomes have suggested that poor tamoxifen adherence contributes to therapeutic failure with an increased risk for poor outcomes.…”

“…Severe adverse events and side effects, or concerns about their development, are certainly likely to cause women to discontinue the treatment (9, 10). There is some evidence that ethnicity, demographic factors, including socioeconomic status, education level, and age, especially extremes of age under 40-45 and over 75-85, have also been linked to lower adherence (14,16,19,(22)(23)(24) (Table 1). Of the 2 pivotal adherence analyses in the adjuvant setting, Partridge and colleagues (14) found that age younger than 45 years or 85 years or older and nonwhite ancestry were the major predictors for poor (<80%) adherence to tamoxifen at 4 years in 2,378 adjuvant patients.…”

Compliance with adjuvant capecitabine in patients with stage II and III colon cancer: comparison of administrative versus medical record data

“…While oral agents pose many notable advantages when compared to conventional parenteral drugs, including enhanced convenience of self‐administration, reduced hospital and societal costs, and improved patient engagement in their own care 1, 2, 3, 4, these benefits must be balanced against growing concerns regarding poor compliance to treatment and its potentially negative impact on outcomes 1, 2, 3, 4, 5, 6. Suboptimal adherence to medications is a commonly recognized problem for many chronic medical conditions, such as hypertension and diabetes mellitus, where it has been shown to compromise drug effectiveness 7, 8, 9, 10.…”

“…The majority of studies on medication compliance in oncology have focused on oral hormonal therapies in breast cancer 5, 6, 11, 12, 13 even though oral drugs are also frequently used in other cancers 14, 15, 16, 17. In colon cancer, the oral 5‐fluorouracil prodrug known as capecitabine is a commonly prescribed component in a large number of systemic therapy regimens 18, 19, but it has received relatively little focus to date 20, 21, 22, 23.…”