Department of Medicine and Clinical Pharmacology, Cardio-Oncology Program, Vanderbilt University Medical Center, 1211 Medical Center Dr, Nashville, TN, USA.
Department of Pharmacology, Sorbonne Université, INSERM CIC Paris-Est, AP-HP, ICAN, Pitié-Salpêtrière Hospital, Paris F-75013, France.
Cardiovasc Res. 2019 Apr 15;115(5):878-894. doi: 10.1093/cvr/cvz020.
Breast and prostate cancers are among the most prevalent cancers worldwide. Oestradiol and progesterone are major drivers for breast cancer proliferation, and androgens for prostate cancer. Endocrine therapies are drugs that interfere with hormone-activated pathways to slow cancer progression. Multiple new breakthrough drugs improving overall survival have recently been developed within this class. As the use of these latter drugs grows, incidence of cardiac arrhythmias has emerged as an unappreciated complication. These changes are not surprising given that sex hormones alter ventricular repolarization. Testosterone shortens action potential duration and QT interval duration, while oestradiol has an opposite effect. In patients with breast cancer, selective oestrogen receptor modulators are associated with more reports for long QT and torsade de pointes (TdP) than aromatase inhibitors, likely through an oestradiol-like effect on the heart. Cyclin-dependent kinase 4/6 inhibitors, a new class of anticancer drugs used in combination with endocrine therapies in hormone receptor positive breast cancer, are also variably associated with drug-induced long QT, particularly with ribociclib. In prostate cancer, androgen deprivation therapy is associated with long QT and TdP, and possibly atrial fibrillation for abiraterone. In this review, we have summarized the clinical and preclinical data focusing on cardiac arrhythmia considerations of hormone cancer therapies.
乳腺癌和前列腺癌是全球最常见的癌症类型之一。雌激素和孕激素是乳腺癌增殖的主要驱动因素，而雄激素是前列腺癌的主要驱动因素。内分泌治疗药物是一类通过干扰激素激活途径来减缓癌症进展的药物。在这一类别中，最近开发了多种新的突破性药物，可提高整体存活率。随着这些药物的使用增加，心律失常的发生率已成为一个未被重视的并发症。鉴于性激素会改变心室复极，这些变化并不奇怪。睾丸激素缩短动作电位持续时间和 QT 间期持续时间，而雌二醇则有相反的作用。在乳腺癌患者中，选择性雌激素受体调节剂与芳香化酶抑制剂相比，与更长的 QT 和尖端扭转型室性心动过速（TdP）报告更多，可能是通过对心脏的类似雌二醇的作用。细胞周期蛋白依赖性激酶 4/6 抑制剂是一类新型的抗癌药物，与激素受体阳性乳腺癌的内分泌治疗联合使用，也与药物诱导的长 QT 有关，特别是与 ribociclib 有关。在前列腺癌中，雄激素剥夺疗法与长 QT 和 TdP 有关，阿比特龙可能与心房颤动有关。在这篇综述中，我们总结了关注激素癌症治疗中心律失常的临床和临床前数据。
