Fourati Nejla, Trigui Rim, Charfeddine Selma, Dhouib Fatma, Kridis Wala Ben, Abid Leila, Khanfir Afef, Mnejja Wafa, Daoud Jamel
Université de Sfax, CHU d'Habib-Bourguiba, faculté de médecine, service de radiothérapie carcinologique, Sfax, Tunisie.
Université de Sfax, CHU d'Habib-Bourguiba, faculté de médecine, service de radiothérapie carcinologique, Sfax, Tunisie.
Bull Cancer. 2021 May;108(5):501-512. doi: 10.1016/j.bulcan.2020.12.012. Epub 2021 Mar 18.
The HER2 receptor (Human Epidermal Growth Receptor 2) is a transmembrane receptor with tyrosine kinase activity that is over-expressed in 25-30 % of breast carcinomas. Its activation is associated with an exaggeration of cell proliferation with an increase in repair capacity resulting in increased radioresistance. On cardiac tissues, HER2 receptor activation plays a cardio-protective role. Trastuzumab, the first anti-HER2 drug used to treat patients with breast cancer overexpressing HER2 receptor , inhibits the cascade of reactions resulting in the proliferation of tumor cells, thus restoring cellular radiosensitivity. However, the combination of Trastuzumab with radiation therapy also removes HER2 receptor cardio-protective role on myocardial cells which increases the risk of cardiotoxicity. Thus, the concomitant association of these two modalities has long been a subject of controversy. Recent advances in radiation therapy technology and early detection of cardiac injury may limit the cardiotoxicity of this combination. Through this review, we developed the biological basis and the benefit-risk of concomitant combination of radiotherapy and Trastuzumab in adjuvant treatment of breast cancers overexpressing HER2 and we discuss the modalities of its optimization.
HER2受体(人表皮生长受体2)是一种具有酪氨酸激酶活性的跨膜受体,在25%-30%的乳腺癌中过度表达。其激活与细胞增殖过度相关,修复能力增强,导致放射抗性增加。在心脏组织上,HER2受体激活发挥心脏保护作用。曲妥珠单抗是第一种用于治疗HER2受体过表达乳腺癌患者的抗HER2药物,它抑制导致肿瘤细胞增殖的反应级联,从而恢复细胞放射敏感性。然而,曲妥珠单抗与放射治疗联合使用也会消除HER2受体对心肌细胞的心脏保护作用,增加心脏毒性风险。因此,这两种治疗方式的联合应用长期以来一直存在争议。放射治疗技术的最新进展和心脏损伤的早期检测可能会限制这种联合治疗的心脏毒性。通过本综述,我们阐述了放疗与曲妥珠单抗联合辅助治疗HER2过表达乳腺癌的生物学基础和利弊,并讨论了其优化方案。