Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.
目的： 评价紫杉醇+卡铂密集化疗联合曲妥珠单抗新辅助治疗Ⅱ~Ⅲ期人表皮生长因子受体2(HER－2)阳性且激素受体(HR)阴性乳腺癌的远期疗效和安全性。 方法： 纳入2013年7月至2019年11月中国医学科学院肿瘤医院肿瘤内科收治的Ⅱ~Ⅲ期HER－2阳性且HR阴性乳腺癌，未手术者予剂量密集PCbH方案(紫杉醇+卡铂剂量密集化疗联合曲妥珠单抗)新辅助治疗，后行根治性手术切除，已手术者予标准辅助治疗[AC－TH方案(表柔比星或吡柔比星+环磷酰胺序贯多西他赛+曲妥珠单抗)或TCbH方案(多西他赛+卡铂联合曲妥珠单抗)]，通过倾向性评分匹配新辅助、辅助治疗两组患者进行生存分析，评估不良反应。 结果： 共入选符合条件的患者166例，其中新辅助治疗组51例，辅助治疗组115例。与辅助治疗组相比，新辅助治疗组患者更年轻(<35岁者分别占19.6%和5.2%，P＝0.014)、肿瘤更大(T3期患者分别占62.7%和7.8%，P<0.001)、分期更晚(ⅡA期者分别占2.0%和41.7%，P<0.001)。49对患者倾向性评分匹配成功，匹配后的新辅助治疗组和辅助治疗组协变量均衡性良好。匹配人群的中位随访时间为46.5个月。新辅助治疗组和辅助治疗组患者的4年无复发生存率分别为73.3%(95% CI：59.0%~87.6%)和80.6%(95% CI：67.9%~93.3%)，4年总生存率分别为91.5%(95% CI：81.7%~100.0%)和97.8%(95% CI：93.5%~100.0%)，差异均无统计学意义(P值分别为0.418和0.314)。新辅助治疗组3~4级中性粒细胞减少的发生率为45.1%(23/51)，低于辅助治疗组的53.9%(62/115)，且心脏安全性更好。 结论： Ⅱ~Ⅲ期HER－2阳性且HR阴性乳腺癌，可选择去蒽环方案新辅助化疗联合抗HER－2靶向治疗，同时应积极探索兼顾疗效与安全的优化药物组合。.
Keywords: Anthracyclines; Breast neoplasms; Dose-dense chemotherapy; Epidermal growth factor receptor-2; Hormone receptor; Neoadjuvant therapy.