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Supplementary editorial provided by OncologySTAT

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Less than half of breast cancer patients who start adjuvant hormonal therapy remain adherent for the full duration of treatment.

EXPERT COMMENTARY

Lee Schwartzberg, MD, Editor-in-Chief

Increasing use of oral therapies in oncology has appropriately focused attention on adherence with dosing over long periods of administration. There is rising concern that, due to cost, side effects, psychosocial issues, and other factors, patients may be compromising their health but not taking medications as prescribed. This study supports this assumption by demonstrating that fully half of patients prescribed hormone therapy for breast cancer are nonadherent over 5 years. Much more effort is necessary to improve provider-patient communication, as well as monitoring and adherence promotion, regarding oral agents. Reliable delivery of active therapy is as important as the actual development of new treatments in order to achieve optimal outcome.

STUDY IN CONTEXT


Adjuvant hormonal therapy with tamoxifen or an aromatase inhibitor (AI) for 5 years significantly reduces recurrence and mortality in women with hormone-sensitive breast cancer. Yet studies show that early discontinuation rates are high, and adherence rates are low, for this potentially life-saving regimen. Previous adherence studies were small and focused primarily on elderly patients. Hershman et al, using the database from Kaiser Permanente of Northern California, studied the problem in a large, diverse population that had equal access to health care and prescription drugs.

The database included more than 15,000 women who were diagnosed with hormone-receptor−positive stage I−III breast cancer between 1996 and 2007. From this cohort, the researchers identified 8769 eligible women who had filled at least one prescription for an AI (anastrozole, exemestane, or letrozole) or tamoxifen, or both, within 12 months of their diagnosis and before any recurrence. The diverse population included ethnic Asians (11%), Hispanics (7.2%), African Americans (5.6%), and whites (76.2%).

Over 4.5 years of follow-up, 2790 (32%) patients discontinued hormonal therapy. Of the 5979 patients who continued, 28% failed to adhere to the regimen (19% of the total). Thus, only 49% of patients were fully adherent for the entire 4.5 years. Rates of discontinuation and nonadherence were similar from year to year.

Significant predictors of early discontinuation included age <50 years and >65 years (vs age 50−65), lumpectomy (vs mastectomy), and more comorbidities. Factors associated with completion of therapy included Asian/Pacific Islander ethnicity, being married, earlier year of diagnosis, receipt of adjuvant chemotherapy or radiotherapy, and longer prescription refill interval.

Factors predicting nonadherence included African American race, lumpectomy, unknown tumor size, lymph node involvement, and more comorbidities. Predictors of full adherence were earlier year of diagnosis, being married, and longer prescription refill interval. Results for both early discontinuation and nonadherence were similar for patients taking tamoxifen or AIs. The authors suggested that shorter refill intervals may be linked to greater nonadherence because of the inconvenience of frequent refilling.

African American patients were more likely than white women to be nonadherent, but there was no difference in discontinuation rates between black and white women. Asian/Pacific Islander women were less likely than other racial/ethnic groups to discontinue therapy, but their nonadherence rates did not differ from those of other groups.

Multivariate analysis using a more refined age categorization showed that patients at the age extremes (<40 years and >75 years) were most likely to discontinue or be nonadherent to therapy, compared with patients age 50 to 65 years. The 202 patients younger than age 40 were the most noncompliant. They were 50% more likely to discontinue therapy and 40% more likely to be nonadherent (P < .001).

Previous studies have also shown low adherence among younger women, but, as the authors note, these findings have received little attention. Younger women with cancer may face greater barriers to adherence since they are less likely to have health insurance; they may have greater psychosocial and medical challenges, since they are more likely to have a delayed diagnosis and less likely to participate in clinical trials.

The greatest barrier to adherence for patients involves poor patient/physician communication upfront, reflected in the fact that 13% of patients were nonadherent from the first refill. The physician may fail to fully explain the benefits of hormonal therapy or prepare patients for adverse events. In this study, 4% of patients filled only one prescription, and the early discontinuation may be related to early treatment toxicities.

Further research is warranted to explore the association between nonadherence to hormonal therapy and breast-cancer–specific mortality. Interventions that help patients adhere to the full course of hormonal therapy are needed, especially for younger women.

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