Risk Factors of QTc Prolongation in Women With Hormone Receptor‒positive/Human Epidermal Growth Factor Receptor 2‒negative Metastatic Breast Cancer: A Retrospective Analysis of Health Care Claims Data

Purpose: In addition to biomarker status, treatment selection for metastatic breast cancer (mBC) includes individual patient and clinical characteristics such as tumor burden, timing of disease recurrence, and comorbidities. Women with mBC may take medications that can increase the risk of drug-induced toxicities, including prolongation of cardiac repolarization (prolongation of QT interval). Corrected QT (QTc) prolongation, a toxicity associated with many cancer treatments, can lead to potentially life-threatening ventricular arrhythmias. As such, it is important to identify patients at risk for QTc prolongation due to comorbid conditions, concomitant medications, or electrolyte abnormalities. This real-world study estimated the proportion of women with hormone receptor‒positive (HR+)/human epidermal growth factor receptor 2‒negative (HER2‒) mBC who may be at risk of developing QTc prolongation. Results in the elderly are also included.

Methods: This retrospective, cross-sectional cohort study used the Truven Health MarketScan and Optum Clinformatics administrative claims databases. Patients' medical and pharmacy data were evaluated to assess the risk of QTc prolongation. Prescription and medication administration claims were evaluated during the 7-day period before the index date (ie, first secondary neoplasm diagnosis). In addition, International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification, codes were evaluated 12 months before the index date to describe congenital long QT syndrome, cardiac disease, and electrolyte abnormalities.

Findings: A cohort of 24,340 women with HR+/HER2‒ mBC were identified, including 5059 women aged 65-74 years and 4851 aged ≥75 years. Based on an overall analysis of risk factors (congenital long QT syndrome, cardiovascular disease, electrolyte abnormalities, or concomitant medications), 29.5% of all patients, 33.2% of patients aged 65-74 years, and 40.5% of patients aged ≥75 years had risk factors for QTc prolongation.

Implications: This analysis of real-world data indicates that almost 1 in 3 women with HR+/HER2‒ mBC had congenital long QT syndrome, cardiovascular disease, and/or electrolyte abnormalities or received a concomitant medication that could increase the risk of developing QTc prolongation. The risk factors for congenital long QT syndrome, cardiovascular disease, or electrolyte abnormalities were more common in older patients. This analysis emphasizes the importance of individualized benefit/risk assessment during treatment decisions, especially when considering drugs with known or possible QTc prolongation risk.