Elshafie Shaimaa, Villa-Zapata Lorenzo, Tackett Randall L, Zaghloul Iman Y, Young Henry N
Department of Clinical and Administrative Pharmacy, College of Pharmacy, University of Georgia, Athens, Georgia, USA.
Central Administration for Drug Control, Egyptian Drug Authority, Cairo, Egypt.
Cancer Med. 2025 Jan;14(1):e70548. doi: 10.1002/cam4.70548.
Emerging evidence suggests potential cardiovascular toxicities from oral endocrine therapies (ETs); however, results are conflicting. This study comprehensively examined adverse reactions of ETs and investigated cardiovascular and metabolic safety signals within the FDA Adverse Event Reporting System (FAERS).
Reports in the FAERS through December 2023 were analyzed for documented reactions to tamoxifen, letrozole, anastrozole, and exemestane in female breast cancer patients. Standardized queries were used to identify cases of cardiovascular (myocardial infarction, heart failure, arrhythmia, stroke) and metabolic (hypertension, dyslipidemia, hyperglycemia) disorders. Descriptive and disproportionality analyses were performed to assess reports and detect safety signals.
Among 14,327 unique ET-related reports, arthralgia (n = 1873 events) was the most prevalent reaction. We identified 2170 cardiovascular and 2252 metabolic events associated with ETs. Letrozole had the highest reporting rate of cardiac arrhythmia (7.7%) and showed positive signals for both arrhythmia (reporting odds ratio [ROR] = 2.2; 95% confidence interval [CI]: 1.8-2.5) and myocardial infarction (ROR = 1.9; 95% CI: 1.4-2.6). We also observed a significantly increased risk of heart failure with letrozole (ROR = 1.3; 95% CI: 1.1-1.6) and stroke with tamoxifen (ROR = 1.7; 95% CI: 1.5-2.1). Only anastrozole was significantly associated with metabolic dysfunctions with a notable hyperglycemia reporting rate of 12.2%.
Our findings provide valuable evidence on common reactions as well as controversial cardiovascular and metabolic abnormalities associated with the real-world use of ETs for breast cancer. Ongoing benefit-risk assessment and close monitoring of cardiac function during treatment, particularly in high-risk women, are warranted to optimize cancer outcomes while minimizing cardiovascular injury.
新出现的证据表明口服内分泌治疗（ETs）可能存在心血管毒性；然而，结果相互矛盾。本研究全面检查了ETs的不良反应，并在FDA不良事件报告系统（FAERS）中调查了心血管和代谢安全信号。
分析了FAERS中截至2023年12月的报告，以了解女性乳腺癌患者对他莫昔芬、来曲唑、阿那曲唑和依西美坦的记录反应。使用标准化查询来识别心血管（心肌梗死、心力衰竭、心律失常、中风）和代谢（高血压、血脂异常、高血糖）疾病的病例。进行描述性和不成比例分析以评估报告并检测安全信号。
在14327份与ET相关的独特报告中，关节痛（n = 1873例）是最常见的反应。我们确定了2170例与ETs相关的心血管事件和2252例代谢事件。来曲唑的心律失常报告率最高（7.7%），并且在心律失常（报告比值比[ROR] = 2.2；95%置信区间[CI]：1.8 - 2.5）和心肌梗死（ROR = 1.9；95% CI：1.4 - 2.6）方面均显示出阳性信号。我们还观察到来曲唑导致心力衰竭的风险显著增加（ROR = 1.3；95% CI：1.1 - 1.6），他莫昔芬导致中风的风险增加（ROR = 1.7；95% CI：1.5 - 2.1）。只有阿那曲唑与代谢功能障碍显著相关，高血糖报告率高达12.2%。
我们的研究结果为与乳腺癌ETs实际应用相关的常见反应以及有争议的心血管和代谢异常提供了有价值的证据。在治疗期间，特别是在高危女性中，持续进行获益 - 风险评估并密切监测心脏功能，对于优化癌症治疗效果同时最小化心血管损伤是必要的。
