Drug interaction among tamoxifen and aromatase inhibitors tied to non adherence to Endocrine Therapy in breast cancer patients: JAMA
Endocrine therapy (ET), which includes tamoxifen and aromatase inhibitors (AI) either alone or in combination with other agents, represents the backbone of therapeutic strategies in the management of patients with hormone receptor (HR)-positive breast cancer. Given that the survival of patients with HR-positive breast cancer is strongly correlated with the use of ET, especially in the adjuvant setting, nonadherence represents a major concern in these patients.
The 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. 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. This study by Elie Rassy and team aimed to explore the PDDI between comedications and ET and investigate their association with adherence to ET.
This cohort study used anonymized health record data of women with breast cancer who received ET in a private observational primary care database. Patients eligible for analysis included women aged 18 years or older who had a reported diagnosis of breast cancer and received ET with tamoxifen or aromatase inhibitor between 1994 and 2021. Data were analyzed 2021.
Adherence to ET during a given year was defined by a medication possession ratio of 80% or greater over 1-year prescription periods. PDDI were categorized into absent, minor (a combination to take into account), moderate (combination requiring precautions for use), major (combination not recommended), and contraindicated according to guidelines in the Claude Bernard Drug Database.
A total of 10,863 patients who were prescribed ET for breast cancer were eligible for the analysis (age 70 years or older, 3509 patients [32.3%]).
In the tamoxifen cohort (3564 patients), PDDI were reported in 497 of 3670 patients (13.5%) at baseline (moderate, 254 patients [51.1%]; major, 227 patients [45.7%]), 2047 of 4831 patients (42.4%) at year 1, 1127 of 2751 patients (41.0%) at year 2, 761 of 1861 patients (40.9%) at year 3, 376 of 1058 patients (35.5%) at year 4, and 201 of 593 patients (33.9%) at year 5.
In the aromatase inhibitor cohort (7299 patients), PDDI were reported in 592 of 7437 patients (8.0%) at baseline (moderate in 588 of 592 patients [99.3%]), which reached 2875 of 9031 patients (31.8%) at year 1 and ranged between 31.4% (1802 of 5730 patients in year 2) and 32.8% (791 of 2411 in year 4) throughout the study period.
No association between adherence and PDDI was found in the tamoxifen (OR, 0.99; 95% CI, 0.91-1.08) or aromatase inhibitor (OR, 1.05; 95% CI, 0.95-1.15) cohort.
Nonadherence to long-term medications is a multifaceted phenomenon in which multiple and complex determinants are involved, including patients' attributes, disease characteristics, and treatment adverse effects. Because weak adherence to ET has been associated with lower breast cancer outcomes and increased direct and indirect health care costs, it is of utmost importance to identify the targetable determinants of nonadherence to set up suitable strategies to prevent ET discontinuation. This study aimed to investigate whether PDDI between comedication and ET was associated with adherence to tamoxifen and AI.
Adherence to ET in patients with breast cancer is a challenge given that factors into recurrence rates and survival. This study expanded on the understanding of nonadherence complexity, providing important insights on the prevalence of PDDI among patients receiving ET for breast cancer. Although PDDI were not significantly associated with adherence over time, these findings highlight the importance of a comprehensive medication assessment at each patient visit to avoid deleterious interactions that may negatively affect survival outcomes.
Source: Elie Rassy, MD, MPH; Aurélie Bardet, PhD; Omar Bougacha; JAMA Network Open. 2022;5(12):e2244849. doi:10.1001/jamanetworkopen.2022.44849
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