Medical Oncology Unit, IRCCS Salvatore Maugeri Foundation, via Maugeri 4, Pavia, Italy.
Breast. 2011 Apr;20(2):176-83. doi: 10.1016/j.breast.2010.11.002. Epub 2010 Dec 13.
Treatment of breast cancer (BC) has changed over the last decade with the advent of targeted therapies. Whereas traditional chemotherapy was directed toward all rapidly dividing cells (cancerous or not), several new anti-cancer drugs are mainly tailored to specific genetic pathways of cancer cells. Ideally, the goal of these new therapies is to improve the management of cancer with a specific targeting of the malignant cell and fewer side effects than traditional chemotherapy. Due to the initial success of this approach, an increasing number of targeted drugs entered into clinical development. However, unanticipated side effects of the new drugs, such as cardiotoxicity and heart failure, emerged from several clinical trials. The mechanisms of cardiotoxicity due to traditional chemotherapy and the one due to new drugs seem to be inherently different. In the case of BC, available targeted therapies are probably associated with the abrogation of normal molecular pathways involved in cardiomyocytes and endothelial cells survival/proliferation. The cardiac safety profile of these new drugs asks for a careful patient monitoring and follow up. Herein we will review the cardiotoxicity of BC patients receiving antiERBB2 treatment (Trastuzumab, Lapatinib), VEGF inhibitors (Bevacizumab) and tirosin-kinase inhibitors (Sorafenib, Sunitinib). We will discuss the molecular mechanisms that underlie the risk of cardiotoxicity, and we will examine the molecular tools useful for prediction of heart failure and for identification of subgroups of BC patients more susceptible to cardiac side effects induced by targeted therapies. Attention will be paid in particular to ERBB2 gene and its polymorphisms, as well as to the possible genetic risk stratification of BC patients. Finally, we will discuss the possible clinical strategies to prevent and minimizing the cardiotoxicity of targeted therapies in BC patients, focusing in particular on new drugs combination and on the emerging role of a tight partnership between cardiologists and oncologists.
过去十年，随着靶向治疗的出现，乳腺癌（BC）的治疗发生了变化。传统化疗针对的是所有快速分裂的细胞（包括癌细胞和非癌细胞），而几种新的抗癌药物主要针对癌细胞的特定遗传途径。理想情况下，这些新疗法的目标是通过特异性靶向恶性细胞并减少传统化疗的副作用来改善癌症的治疗。由于这种方法的初步成功，越来越多的靶向药物进入了临床开发。然而，一些临床试验中出现了新药物意料之外的副作用，如心脏毒性和心力衰竭。传统化疗和新药物引起的心脏毒性的机制似乎本质上不同。在 BC 的情况下，现有的靶向疗法可能与参与心肌细胞和内皮细胞存活/增殖的正常分子途径的中断有关。这些新药的心脏安全性要求对患者进行仔细的监测和随访。在此，我们将回顾接受抗 ERBB2 治疗（曲妥珠单抗、拉帕替尼）、VEGF 抑制剂（贝伐单抗）和酪氨酸激酶抑制剂（索拉非尼、舒尼替尼）的 BC 患者的心脏毒性。我们将讨论导致心脏毒性的分子机制，并研究有助于预测心力衰竭和确定对靶向治疗引起的心脏副作用更敏感的 BC 患者亚组的分子工具。特别关注 ERBB2 基因及其多态性，以及 BC 患者的可能遗传风险分层。最后，我们将讨论预防和最小化 BC 患者靶向治疗心脏毒性的可能临床策略，特别关注新药联合以及心脏病专家和肿瘤专家之间紧密合作的新兴作用。
