低风险乳腺癌辅助化疗：4周期 vs 6周期

一项最近的多中心临床研究表明，对于早期乳腺癌手术切除后，在4个周期的辅助化疗基础上增加2个周期不会改善无复发生存率（RFS），该研究在线发表在JCO杂志上。
对于低风险原发性乳腺癌病人来说，辅助化疗的最佳周期还尚未可知。癌症和白血病组B试验40101进行了一项III期因子设计去确定6个周期化疗方案是否优于4个周期。同时也试图确定紫杉醇（T）的疗效是否与阿霉素/环磷酰胺（AC）相当，但是毒性更小。


      在2002到2008年间，研究纳入了3171名可手术的乳腺癌患者，94%为淋巴结阴性，6%为1~3个淋巴结阳性。随机分配接受4或6个周期的AC或T的辅助化疗。中位随访5.3年，6个周期和4个周期的4年RFS分别为90.9%和91.8%，调整的危险比（HR）为1.03（95%CI，0.84~1.28；P=0.77）。4年OS分别为95.3%和96.3%（HR，1.12；P=0.44）。


      本研究没有公布紫杉醇和阿霉素/环磷酰胺比较的数据，但是安全监测委员会告知研究者说治疗类型和生存率之间没有交互作用。
文献标题：Six Cycles of Doxorubicin and Cyclophosphamide or Paclitaxel Are Not Superior to Four Cycles As Adjuvant Chemotherapy for Breast Cancer in Women With Zero to Three Positive Axillary Nodes

摘要：
Purpose The ideal duration of adjuvant chemotherapy for patients with lower risk primary breast cancer is not known. Cancer and Leukemia Group B trial 40101 was conducted using a phase III factorial design to define whether six cycles of a chemotherapy regimen are superior to four cycles. We also sought to determine whether paclitaxel (T) is as efficacious as doxorubicin/cyclophosphamide (AC), but with reduced toxicity.


Patients And Methods Between 2002 and 2008, the study enrolled women with operable breast cancer and zero to three positive nodes. Patients were randomly assigned to either four or six cycles of either AC or T. Study stratifiers were estrogen receptor/progesterone receptor (ER/PgR), human epidermal growth factor receptor 2 (HER2), and menopausal status. After 2003, all treatment was administered in dose-dense fashion. The primary efficacy end point was relapse-free survival (RFS).


Results A total of 3,171 patients were enrolled; 94% were node-negative and 6% had one to three positive nodes. At a median follow-up of 5.3 years, the 4-year RFS was 90.9% and 91.8% for six and four cycles, respectively. The adjusted hazard ratio (HR) of six to four cycles regarding RFS was 1.03 (95% CI, 0.84 to 1.28; P = .77). The 4-year OS was 95.3% and 96.3% for six and four cycles, respectively, with an HR of six to four cycles of 1.12 (95% CI, 0.84 to 1.49; P = .44). There was no interaction between treatment duration and chemotherapy regimen, ER/PgR, or HER2 status on RFS or OS.


Conclusion For women with resected primary breast cancer and zero to three positive nodes, we found no evidence that extending chemotherapy regimens of AC or single-agent T from four to six cycles improves clinical outcome.