Slamon D J, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L
Division of Hematology and Oncology, UCLA School of Medicine, Los Angeles, Calif 90095-1678, USA.
N Engl J Med. 2001 Mar 15;344(11):783-92. doi: 10.1056/NEJM200103153441101.
The HER2 gene, which encodes the growth factor receptor HER2, is amplified and HER2 is overexpressed in 25 to 30 percent of breast cancers, increasing the aggressiveness of the tumor.
We evaluated the efficacy and safety of trastuzumab, a recombinant monoclonal antibody against HER2, in women with metastatic breast cancer that overexpressed HER2. We randomly assigned 234 patients to receive standard chemotherapy alone and 235 patients to receive standard chemotherapy plus trastuzumab. Patients who had not previously received adjuvant (postoperative) therapy with an anthracycline were treated with doxorubicin (or epirubicin in the case of 36 women) and cyclophosphamide alone (138 women) or with trastuzumab (143 women). Patients who had previously received adjuvant anthracycline were treated with paclitaxel alone (96 women) or paclitaxel with trastuzumab (92 women).
The addition of trastuzumab to chemotherapy was associated with a longer time to disease progression (median, 7.4 vs. 4.6 months; P<0.001), a higher rate of objective response (50 percent vs. 32 percent, P<0.001), a longer duration of response (median, 9.1 vs. 6.1 months; P<0.001), a lower rate of death at 1 year (22 percent vs. 33 percent, P=0.008), longer survival (median survival, 25.1 vs. 20.3 months; P=0.01), and a 20 percent reduction in the risk of death. The most important adverse event was cardiac dysfunction of New York Heart Association class III or IV, which occurred in 27 percent of the group given an anthracycline, cyclophosphamide, and trastuzumab; 8 percent of the group given an anthracycline and cyclophosphamide alone; 13 percent of the group given paclitaxel and trastuzumab; and 1 percent of the group given paclitaxel alone. Although the cardiotoxicity was potentially severe and, in some cases, life-threatening, the symptoms generally improved with standard medical management.
Trastuzumab increases the clinical benefit of first-line chemotherapy in metastatic breast cancer that overexpresses HER2.
HER2基因编码生长因子受体HER2，在25%至30%的乳腺癌中发生扩增且HER2过表达，从而增加肿瘤的侵袭性。
我们评估了针对HER2的重组单克隆抗体曲妥珠单抗对HER2过表达的转移性乳腺癌女性患者的疗效和安全性。我们将234例患者随机分配至仅接受标准化疗组，235例患者随机分配至接受标准化疗加曲妥珠单抗组。既往未接受过蒽环类辅助（术后）治疗的患者，单用多柔比星（36例女性患者使用表柔比星）和环磷酰胺进行治疗（138例女性患者），或联合曲妥珠单抗治疗（143例女性患者）。既往接受过蒽环类辅助治疗的患者，单用紫杉醇进行治疗（96例女性患者），或紫杉醇联合曲妥珠单抗治疗（92例女性患者）。
化疗加用曲妥珠单抗与疾病进展时间延长相关（中位数分别为7.4个月和4.6个月；P<0.001），客观缓解率更高（50%对32%，P<0.001），缓解持续时间更长（中位数分别为9.1个月和6.1个月；P<0.001），1年时死亡率更低（22%对33%，P=0.008），总生存期更长（中位生存期分别为25.1个月和20.3个月；P=0.01），死亡风险降低20%。最重要的不良事件是纽约心脏协会III或IV级心脏功能障碍，在接受蒽环类、环磷酰胺和曲妥珠单抗治疗的患者中发生率为27%；仅接受蒽环类和环磷酰胺治疗的患者中发生率为8%；接受紫杉醇和曲妥珠单抗治疗的患者中发生率为13%；仅接受紫杉醇治疗的患者中发生率为1%。尽管心脏毒性可能很严重，在某些情况下甚至危及生命，但通过标准的药物治疗，症状通常会改善。
曲妥珠单抗可增加HER2过表达的转移性乳腺癌一线化疗的临床获益。
