Lin Amy, Rugo Hope S
Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Curr Treat Options Oncol. 2007 Feb;8(1):47-60. doi: 10.1007/s11864-007-0008-2.
Treatment of early stage breast cancer requires a multimodality approach in order to eradicate residual cancer and prevent recurrent disease. Targeting the pathways that promote or sustain cancer cell growth and invasion is critical to the effective treatment of breast and other cancers. Overexpression of the family of HER receptors have been associated with a variety of malignancies; the first and best studied is the association of overexpression of the HER2/neu receptor with a more aggressive breast cancer phenotype and poorer survival. A humanized antibody to HER2/neu, trastuzumab, is now FDA approved for the treatment of early stage, HER2/neu overexpressing breast cancer sequenced with chemotherapy including doxorubicin, cyclophosphamide, and paclitaxel. Additional international and national studies support the significant impact of trastuzumab on both disease free and overall survival in women with this aggressive form of breast cancer. Toxicity includes a low but clear risk of congestive heart failure, and the large phase III trials have helped to determine which patients are at higher risk for this complication. Non-anthracycline containing regimens are an alternative therapy associated with reduced cardiac toxicity. Trastuzumab therapy is now the standard of care for the treatment of early stage, HER2/neu positive breast cancer given in combination with one of several chemotherapy regimens. Ongoing questions include the appropriate duration of trastuzumab treatment as well as the optimal chemotherapy regimen and sequence. The next large phase III adjuvant trial for this subset of breast cancer is an international collaboration designed to evaluate the added or alternative benefit of an oral tyrosine kinase inhibitor targeting HER2/neu as well as the epidermal growth factor receptor (EGFR), lapatinib. Other trials are investigating differences in duration. Studies in the neoadjuvant setting should help to define markers of trastuzumab and lapatinib sensitivity and resistance. Preliminary data combining trastuzumab with the antiangiogenic antibody bevacizumab is encouraging; this combination will be tested in both early stage and late stage disease.
早期乳腺癌的治疗需要采用多模式方法，以根除残留癌症并预防疾病复发。针对促进或维持癌细胞生长和侵袭的途径对于乳腺癌和其他癌症的有效治疗至关重要。HER受体家族的过表达与多种恶性肿瘤相关；研究最早且最为深入的是HER2/neu受体过表达与侵袭性更强的乳腺癌表型及较差生存率之间的关联。一种针对HER2/neu的人源化抗体——曲妥珠单抗，现已获美国食品药品监督管理局（FDA）批准，用于治疗早期、HER2/neu过表达的乳腺癌，可与包括阿霉素、环磷酰胺和紫杉醇在内的化疗联合使用。更多国际和国内研究证实，曲妥珠单抗对这种侵袭性乳腺癌女性患者的无病生存期和总生存期均有显著影响。其毒性包括虽低但明确的充血性心力衰竭风险，大型III期试验有助于确定哪些患者发生这种并发症的风险更高。不含蒽环类药物的方案是一种可降低心脏毒性的替代疗法。曲妥珠单抗治疗现已成为早期HER2/neu阳性乳腺癌联合几种化疗方案之一的标准治疗方法。目前仍存在的问题包括曲妥珠单抗治疗的合适时长以及最佳化疗方案和顺序。针对这一乳腺癌亚组的下一项大型III期辅助试验是一项国际合作研究，旨在评估一种靶向HER2/neu以及表皮生长因子受体（EGFR）的口服酪氨酸激酶抑制剂——拉帕替尼的附加或替代益处。其他试验正在研究治疗时长的差异。新辅助治疗的研究应有助于确定曲妥珠单抗和拉帕替尼敏感性及耐药性的标志物。曲妥珠单抗与抗血管生成抗体贝伐单抗联合使用的初步数据令人鼓舞；这种联合疗法将在早期和晚期疾病中进行测试。
