Villejuif, France—How does the potential for drug-drug interactions (PDDI) affect adherence to endocrine therapy among patients with breast cancer?

A new French study from University Paris-Saclay examined a cohort of 10,863 patients who were prescribed endocrine therapy for breast cancer and attempted to determine the answer.

The results indicated PDDIs were not associated with the adherence to endocrine therapy in the tamoxifen or aromatase-inhibitor (AI) cohort. The study team found no statistically significant differences between the different PDDI categories compared with no PDDI.

“While these results suggest that PDDI are not associated with adherence to endocrine therapy over time, the considerable proportion of patients with PDDI warrants comprehensive medication assessment at each patient visit to avoid deleterious interactions,” the authors advised in an article published in the Journal of the American Medical Association Network Open.

The study is significant because higher hospitalization rates and greater healthcare costs can occur with suboptimal adherence to endocrine therapy (ET) among patients with hormone receptor (HR)–positive breast cancer. “Weak adherence to long-term treatments has multiple determinants, including disease characteristics, treatment adverse effects, and patients’ attributes, such as age and comorbidities,” according to the researchers.

Anonymized health record data of women with breast cancer who received ET between 1994 and 2001 were obtained from a private observational primary care database. Eligible for analysis were 10,863 patients who were prescribed ET for breast cancer; of those, 3,509 patients were aged 70 years or older. The data were analyzed in 2021.

According to guidelines in the Claude Bernard Drug Database, adherence to ET during a given year was defined by a medication possession ratio of 80% or greater over 1-year prescription periods. At the same time, PDDI were categorized into absent, minor (a combination to consider), moderate (combination requiring precautions for use), major (combination not recommended), and contraindicated.

The results indicated that, in the tamoxifen cohort, which involved 3,564 patients, PDDI were reported in 13.5% at baseline. Of those, slightly more than one-half were moderate and slightly less than one-half were major. The greatest risk occurred in Year 1 (42.7%), and then declined steadily to about 33.9% in Year 5.

In the AI cohort, which involved 7,299 patients, PDDI were reported in 8.0% of patients at baseline and were moderate in nearly all of them. The rates were similar from Years 1 through 4 at slightly more than 30%.

“In this cohort of patients with hormone-receptor-positive breast cancer, PDDI with tamoxifen and aromatase inhibitors were not associated with adherence to ET,” the authors concluded.

ET, which includes tamoxifen and AIs either alone or in combination with other agents, is the go-to therapeutic strategy to manage patients with HR-positive breast cancer. The researchers advised that weak adherence to ET has been associated with multiple determinants, including extremes of age, low socioeconomic status, limited information about the benefit of adjuvant ET, and intolerable adverse events—mainly menopausal symptoms.

“Polypharmacy and drug interactions are often overlooked even though they can be encountered in 50% to 91% of patients with breast cancer and can be associated with medication nonadherence, and with mortality among patients with cancer,” the authors noted. “It has also been reported that specific medication classes were associated with adherence to ET among patients with breast cancer. Although in this case, the patient’s personal attitude to adherence and the mitigation of ET adverse effects by comedications may play a key role in adherence to ET, potential drug-drug interactions (PDDI) may cause significant morbidity and compromise adherence by enhancing drug toxicity. Thus, a comprehensive understanding of drug interactions is central to optimizing patient adherence to ET through the implementation of personalized strategies.”

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