Department of Medical Oncology, Gustave Roussy, University Paris-Saclay, Villejuif, France.
Department of Biostatistics and Epidemiology, Gustave Roussy, University Paris-Saclay, Villejuif, France.
JAMA Netw Open. 2022 Dec 1;5(12):e2244849. doi: 10.1001/jamanetworkopen.2022.44849.
Suboptimal adherence to endocrine therapy (ET) among patients with hormone-receptor-positive breast cancer significantly affects survival outcomes and is associated with higher hospitalization rates and health care costs. Weak adherence to long-term treatments has multiple determinants, including disease characteristics, treatment adverse effects, and patients' attributes, such as age and comorbidities.
To examine whether potential drug-drug interactions (PDDI) with tamoxifen or aromatase inhibitor were associated with adherence to ET in patients with early and advanced breast cancer.
DESIGN, SETTING, AND PARTICIPANTS: 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.
We used regression models to estimate odds ratios (ORs) and 95% CIs for the associations between adherence and age, baseline comorbidities, PDDI, and adherence to ET during the previous year.
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.
In this cohort of patients with hormone-receptor-positive breast cancer, PDDI with tamoxifen and aromatase inhibitors were not associated with adherence to ET.
激素受体阳性乳腺癌患者内分泌治疗（ET）依从性差会显著影响生存结局，并与更高的住院率和医疗保健费用相关。长期治疗的依从性差有多种决定因素，包括疾病特征、治疗不良反应以及患者的年龄和合并症等属性。
研究潜在的与他莫昔芬或芳香化酶抑制剂的药物-药物相互作用（PDDI）是否与早期和晚期乳腺癌患者 ET 依从性相关。
设计、设置和参与者：这项队列研究使用了私人观察性初级保健数据库中接受 ET 的乳腺癌女性的匿名健康记录数据。符合分析条件的患者包括年龄在 18 岁及以上、有报告的乳腺癌诊断且在 1994 年至 2021 年间接受他莫昔芬或芳香化酶抑制剂 ET 的女性。数据于 2021 年进行分析。
在给定的一年中，通过在 1 年的处方期间药物占有比达到 80%或更高来定义 ET 的依从性。根据 Claude Bernard 药物数据库中的指南，将 PDDI 分为不存在、轻微（需要考虑的组合）、中度（需要谨慎使用的组合）、严重（不推荐的组合）和禁忌。
我们使用回归模型估计了与依从性相关的比值比（OR）和 95%置信区间（CI），这些因素包括年龄、基线合并症、PDDI 和前一年的 ET 依从性。
共有 10863 名接受 ET 治疗乳腺癌的患者符合分析条件（年龄 70 岁或以上，3509 名患者[32.3%]）。在他莫昔芬队列（3564 名患者）中，3670 名患者中有 497 名（13.5%）在基线时报告有 PDDI（中度，254 名[51.1%]；严重，227 名[45.7%]），4831 名患者中有 2047 名（42.4%）在第 1 年，2751 名患者中有 1127 名（41.0%）在第 2 年，1861 名患者中有 761 名（40.9%）在第 3 年，1058 名患者中有 376 名（35.5%）在第 4 年，593 名患者中有 201 名（33.9%）在第 5 年。在芳香化酶抑制剂队列（7299 名患者）中，7437 名患者中有 592 名（8.0%）在基线时报告有 PDDI（588 名[99.3%]为中度），在第 1 年达到 2875 名（31.8%），在整个研究期间，范围在 31.4%（第 2 年 5730 名患者中的 1802 名）到 32.8%（第 4 年 2411 名患者中的 791 名）。在他莫昔芬（OR，0.99；95%CI，0.91-1.08）或芳香化酶抑制剂（OR，1.05；95%CI，0.95-1.15）队列中，均未发现 PDDI 与依从性之间存在关联。
在这项接受激素受体阳性乳腺癌治疗的患者队列中，他莫昔芬和芳香化酶抑制剂的 PDDI 与 ET 依从性无关。
