Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials
Authors: Bernard Asselain, William Barlow, John Bartlett, Jonas Bergh, Elizabeth Bergsten-Nordström, 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 Sölkner, 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
Journal: The Lancet Oncology (2017)

<h2>Summary</h2><h3>Background</h3> 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. <h3>Methods</h3> 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). <h3>Findings</h3> 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 <i>vs</i> 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 <i>vs</i> 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92–1·14]; p=0·66), breast cancer mortality (34·4% <i>vs</i> 33·7%; 1·06 [0·95–1·18]; p=0·31), or death from any cause (40·9% <i>vs</i> 41·2%; 1·04 [0·94–1·15]; p=0·45). <h3>Interpretation</h3> 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. <h3>Funding</h3> Cancer Research UK, British Heart Foundation, UK Medical Research Council, and UK Department of Health.