Guiu S, Coudert B, Favier L, Arnould L, Fumoleau P
Département d'oncologie médicale, centre de lutte contre le cancer Georges-François-Leclerc, 1, rue Professeur-Marion, 21000 Dijon, France.
Bull Cancer. 2010 Mar;97(3):365-83. doi: 10.1684/bdc.2010.1040.
HER2-positive breast cancer accounts for 20 to 25% of breast cancers. The surexpression of this tyrosine-kinase receptor is often associated with a poor prognosis. However, the management and the outcome of these patients have changed these last ten years with trastuzumab. Despite the encouraging results obtained with this humanized monoclonal antibody directed against the HER2-receptor, used alone or in association with chemotherapy in metastatic patients, progression under trastuzumab are usually observed and resistances to this treatment are described. Thus, many other monoclonal antibodies and tyrosine-kinase inhibitors emerged. These therapeutics, used alone or in association with chemotherapy or trastuzumab have variable properties: anti-HER2 and anti-EGFR such as lapatinib, pertuzumab and neratinib; anti-EGFR such as erlotinib and gefitinib; antiangiogenesis (bevacizumab, pazopanib); anti-mTOR pathway (temsirolimus, everolimus) or inhibitor of HSP90 (tanespimycine). In this paper, we present an overview on validated targeted therapies and those which are currently under investigation and seem promising in first line or after progression under trastuzumab. Data regarding cardiotoxicity and the use of trastuzumab under particular clinical circumstances (brain metastases, pregnancy) are also reviewed.
人表皮生长因子受体2（HER2）阳性乳腺癌占所有乳腺癌的20%至25%。这种酪氨酸激酶受体的过表达通常与预后不良相关。然而，在过去十年中，随着曲妥珠单抗的应用，这些患者的治疗和预后发生了改变。尽管这种针对HER2受体的人源化单克隆抗体在单独使用或与转移性患者的化疗联合使用时取得了令人鼓舞的结果，但通常会观察到在曲妥珠单抗治疗下病情进展，并且出现了对这种治疗的耐药性。因此，出现了许多其他单克隆抗体和酪氨酸激酶抑制剂。这些治疗药物单独使用或与化疗或曲妥珠单抗联合使用时具有不同的特性：抗HER2和抗表皮生长因子受体（EGFR），如拉帕替尼、帕妥珠单抗和来那替尼；抗EGFR，如厄洛替尼和吉非替尼；抗血管生成（贝伐单抗、帕唑帕尼）；抗雷帕霉素靶蛋白（mTOR）通路（替西罗莫司、依维莫司）或热休克蛋白90（HSP90）抑制剂（坦西莫司）。在本文中，我们概述了已得到验证的靶向治疗药物以及目前正在研究且在一线治疗或曲妥珠单抗治疗进展后似乎有前景的药物。还综述了有关心脏毒性以及在特殊临床情况（脑转移、妊娠）下使用曲妥珠单抗的数据。
