乳腺癌术前化疗局部复发率高？
早期乳腺癌术前与术后化疗的长期结局
十项随机研究个体患者数据的荟萃分析
早期乳腺癌术前新辅助化疗可以提高保乳手术可行性，并且与术后给予相同化疗相比，更有可能清除微转移病变，但是早期乳腺癌术前与术后化疗相比，长期结局尚不明确。
2017年12月11日，英国《柳叶刀》肿瘤学在线发表早期乳腺癌研究者协作组（EBCTCG）早期乳腺癌术前新辅助化疗与术后辅助化疗相关十项随机研究长期结局的个体患者数据协作荟萃分析，对新辅助化疗的长期获益与风险以及肿瘤特征对结局的影响进行了调查。该研究由英国卫生部、英国医学研究理事会、英国心脏基金会、英国癌症研究中心提供资助。
该研究纳入2005年之前开始的10项早期乳腺癌随机研究，获得4756例女性的随机分组前肿瘤特征、临床肿瘤反应、手术、复发和死亡信息，并对新辅助化疗与同样方案术后化疗进行比较。所有患者均未接受靶向治疗，缺乏具体完整的放疗、淋巴结状态、腋窝手术数据。主要结局指标为肿瘤反应、局部治疗范围、局部和远处复发、乳腺癌相关死亡和总死亡率。使用标准回归（对保乳治疗率和反应）和对数秩方法（对复发和死亡率）进行意向治疗分析。
10项EBCTCG早期乳腺癌随机研究
加拿大不列颠哥伦比亚癌症中心（BCCA Vancouver）
法国波尔多研究所（IB Bordeaux）
法国居里研究所(Institut Curie S6)
美国外科辅助协作组（NSABP B-18）
美国国家癌症研究所（NCI Bethesda）
英国伦敦圣乔治医院（St George's London）
英国皇家马斯登医院（RMH London）
奥地利乳腺癌研究协作组（BCSG VII）
欧洲癌症治疗研究组织（EORTC 10902）
欧洲可手术乳腺癌协作研究（ECTO Italy）
结果发现：
入组时间：1983～2002年
中位随访：9年（四分位距：5～14）
末次随访：2013年
化疗方案：以蒽环为主（81%）
临床缓解：新辅助治疗超过2/3（69%）
保乳治疗：新辅助高于辅助（64.8%比49.0%，P<0.0001）
局部复发：新辅助高于辅助（21.4%比15.9%，P=0.0001）
远处复发：新辅助接近辅助（38.2%比38.0%，P=0.66）
乳癌死亡：新辅助接近辅助（34.4%比33.7%，P=0.31）
全因死亡：新辅助接近辅助（40.9%比41.2%，P=0.45）
因此，通过术前新辅助化疗缩小的肿瘤，在保乳治疗后，其局部复发率可能高于未接受术前新辅助化疗治疗的相同大小肿瘤，应该考虑减少局部复发的策略，例如仔细的肿瘤定位、详细的病理学评定、适当的放疗。
对此，荷兰莱顿大学医学中心外科发表同期评论：乳腺癌新辅助化疗不止缩小肿瘤。2007年，《英国外科杂志》曾经发表该中心外科对14项随机研究5500例新辅助和辅助化疗女性的荟萃分析，发现新辅助与辅助化疗相比，总生存、局部复发相似，乳房切除、不良反应较少。EBCTCG的荟萃分析虽然具有里程碑意义，但是缺乏具体完整的放疗、淋巴结状态、腋窝手术等化疗效果影响因素数据。因此，根据EBCTCG的荟萃分析，对于大肿瘤患者可以推荐新辅助化疗，并根据缓解情况推荐后续的保乳手术。建议开展进一步研究，根据新辅助化疗缓解情况，调整乳房和腋窝局部治疗的最佳范围。
Lancet Oncol. 2017 Dec 11. [Epub ahead of print]
Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials.
Bernard Asselain, William Barlow, John Bartlett, Jonas Bergh, Elizabeth Bergsten-Nordstrom, Judith Bliss, Francesco Boccardo, Clare Boddington, Jan Bogaerts, Gianni Bonadonna, Rosie Bradley, Etienne Brain, Jeremy Braybrooke, Philippe Broet, John Bryant, Julie Burrett, David Cameron, Mike Clarke, Alan Coates, Robert Coleman, Raoul Charles Coombes, Candace Correa, Joe Costantino, Jack Cuzick, David Danforth, Nancy Davidson, Christina Davies, Lucy Davies, Angelo Di Leo, David Dodwell, Mitch Dowsett, Fran Duane, Vaughan Evans, Marianne Ewertz, Bernard Fisher, John Forbes, Leslie Ford, Jean-Claude Gazet, Richard Gelber, Lucy Gettins, Luca Gianni, Michael Gnant, Jon Godwin, Aron Goldhirsch, Pamela Goodwin, Richard Gray, Daniel Hayes, Catherine Hill, James Ingle, Reshma Jagsi, Raimund Jakesz, Sam James, Wolfgang Janni, Hui Liu, Zulian Liu, Caroline Lohrisch, Sibylle Loibl, Liz MacKinnon, Andreas Makris, Eleftherios Mamounas, Gurdeep Mannu, Miguel Martín, Simone Mathoulin, Louis Mauriac, Paul McGale, Theresa McHugh, Philip Morris, Hirofumi Mukai, Larry Norton, Yasuo Ohashi, Ivo Olivotto, Soon Paik, Hongchao Pan, Richard Peto, Martine Piccart, Lori Pierce, Philip Poortmans, Trevor Powles, Kathy Pritchard, Joseph Ragaz, Vinod Raina, Peter Ravdin, Simon Read, Meredith Regan, John Robertson, Emiel Rutgers, Suzy Scholl, Dennis Slamon, Lidija Solkner, Joseph Sparano, Seth Steinberg, Rosemary Sutcliffe, Sandra Swain, Carolyn Taylor, Andrew Tutt, Pinuccia Valagussa, Cornelis van de Velde, Jos van der Hage, Giuseppe Viale, Gunter von Minckwitz, Yaochen Wang, Zhe Wang, Xiang Wang, Tim Whelan, Nicholas Wilcken, Eric Winer, Norman Wolmark, William Wood, Milvia Zambetti, Jo Anne Zujewski.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG).
Background: 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.
Methods: 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).
Findings: 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).
Interpretation: 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.
Funding: Cancer Research UK, British Heart Foundation, UK Medical Research Council, UK Department of Health.
DOI: 10.1016/S1470-2045(17)30777-5
Lancet Oncol. 2017 Dec 11. [Epub ahead of print]
Neoadjuvant chemotherapy in breast cancer: more than just downsizing.
Marloes G M Derks, Cornelis J H van de Velde.
Leiden University Medical Center, Leiden, Netherlands.
With the evidence generated from this meta-analysis, patients with large tumours can be recommended to have NACT and subsequent breast-conserving surgery depending on response assessment. Further studies will tailor the optimum extent of breast and axillary treatment on the basis of response to NACT.
DOI: 10.1016/S1470-2045(17)30914-2