Nabholtz Jean-Marc, Reese David M, Lindsay Mary-Ann, Riva Alessandro
Cancer Therapy Development Program and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, 90095, USA.
Clin Breast Cancer. 2002 Oct;3 Suppl 2:S75-9. doi: 10.3816/cbc.2002.s.016.
HER2 gene amplification occurs in approximately 20% of primary breast cancers and is associated with a poor prognosis. Recently, trastuzumab, a humanized murine monoclonal antibody directed against the extracellular domain of HER2, was introduced for the treatment of patients with HER2-overexpressing advanced breast cancer. Trastuzumab has activity as both a single agent and in combination with chemotherapy. However, trastuzumab in conjunction with anthracyclines produces an unacceptably high rate of cardiac toxicity, which has prompted the search for alternative regimens. Docetaxel and the platinum salts are logical candidates to be combined with trastuzumab since these agents exhibit potent synergy with the antibody in preclinical experiments. Furthermore, the available phase II clinical data using the TCH (docetaxel/platinum/trastuzumab) regimen suggest this combination has significant activity. The Breast Cancer International Research Group (BCIRG) 006 trial is a 3-arm adjuvant study comparing doxorubicin/cyclophosphamide followed by docetaxel, the same regimen with trastuzumab administered with docetaxel (TH), and TCH in 3150 women with node-positive or high-risk node-negative, HER2-positive breast cancer. BCIRG 007 compares TH and TCH as first-line therapy in patients with HER2-positive metastatic breast cancer. In both trials, entry is restricted to patients whose tumors are positive for HER2 gene amplification as determined by fluorescence in situ hybridization. The data from these trials, in addition to the results from other ongoing randomized studies, will help define the optimal way to utilize trastuzumab in the management of patients with HER2-positive breast cancer.
HER2基因扩增发生在约20%的原发性乳腺癌中，并与预后不良相关。最近，曲妥珠单抗，一种针对HER2细胞外结构域的人源化鼠单克隆抗体，被引入用于治疗HER2过表达的晚期乳腺癌患者。曲妥珠单抗作为单一药物以及与化疗联合使用均具有活性。然而，曲妥珠单抗与蒽环类药物联合使用会产生不可接受的高心脏毒性发生率，这促使人们寻找替代方案。多西他赛和铂盐是与曲妥珠单抗联合使用的合理候选药物，因为这些药物在临床前实验中与该抗体表现出强大的协同作用。此外，使用TCH（多西他赛/铂/曲妥珠单抗）方案的现有II期临床数据表明这种联合具有显著活性。乳腺癌国际研究组（BCIRG）006试验是一项三臂辅助研究，比较了阿霉素/环磷酰胺序贯多西他赛、相同方案联合曲妥珠单抗与多西他赛（TH）以及TCH，共纳入3150例HER2阳性、淋巴结阳性或高危淋巴结阴性的乳腺癌女性患者。BCIRG 007试验比较了TH和TCH作为HER2阳性转移性乳腺癌患者的一线治疗方案。在这两项试验中，入组仅限于通过荧光原位杂交确定肿瘤HER2基因扩增阳性的患者。这些试验的数据，以及其他正在进行的随机研究的结果，将有助于确定在HER2阳性乳腺癌患者管理中使用曲妥珠单抗的最佳方式。
