Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials.
Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials.
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DOI：
10.1016/s1470-2045(17)30777-5
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发表时间：
2018-01
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通讯作者：
Early Breast Cancer Trialists' Collaborative Group (EBCTCG)
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作者：
Early Breast Cancer Trialists' Collaborative Group (EBCTCG)
早期乳腺癌的新辅助化疗（NACT）可以使保乳手术更加可行，并且可能比术后给予相同的化疗更有可能根除微转移性疾病。我们对来自相关随机试验的个体患者数据进行了协作荟萃分析，研究了NACT的长期获益和风险以及肿瘤特征对结局的影响。我们获得了2005年前开始的10项早期乳腺癌随机试验中4756名妇女的随机化前肿瘤特征、临床肿瘤反应、手术、复发和死亡率的信息，并将NACT与术后给予的相同化疗进行了比较。主要结局是肿瘤缓解、局部治疗程度、局部和远处复发、乳腺癌死亡和总体死亡率。意向性治疗分析采用标准回归法（针对保乳治疗的反应和频率）和对数秩法（针对复发和死亡率）。患者从1983年至2002年进入试验，中位随访时间为9年（IQR 5-14），最后一次随访时间为2013年。大多数化疗以蒽环类药物为基础（3838/4756例[81%]）。超过三分之二（1349 [69%]的1947）分配NACT的妇女有完全或部分临床反应。接受NACT治疗的患者接受保乳治疗的频率增加（接受NACT治疗的2320例患者中有1504例[65%]，接受辅助化疗的2318例患者中有1135例[49%]）。与辅助化疗相比，NACT与更频繁的局部复发相关：NACT的15年局部复发率为21.4%，而辅助化疗为15.9%（增加5.5%[95%CI 2.4 - 8.6];率比1.37 [95%CI 1.17 - 1.61]; p= 0.0001）。NACT和辅助化疗之间的远处复发无显著差异（NACT组15年风险为38.2%，辅助化疗组为38.0%;率比1.02 [95% CI 0.92 - 1.14]; p= 0.66），乳腺癌死亡率（34.4% vs 33.7%; 1.06 [0.95 - 1.18]; p= 0.31）或全因死亡（40.9% vs 41.2%; 1.04 [0.94 - 1.15]; p= 0.45）。与未接受NACT治疗的相同大小的肿瘤相比，NACT缩小的肿瘤在保乳治疗后的局部复发率可能更高。应考虑NACT缩小的肿瘤行保乳治疗后减少局部复发的策略，例如仔细的肿瘤定位、详细的病理评估和适当的放疗。英国癌症研究中心、英国心脏基金会、英国医学研究理事会和英国卫生部。
Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5–14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4–8·6]; rate ratio 1·37 [95% CI 1·17–1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92–1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95–1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94–1·15]; p=0·45). Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered—eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy. Cancer Research UK, British Heart Foundation, UK Medical Research Council, and UK Department of Health.