Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Early Breast Cancer Trialists' Collaborative Group (EBCTCG)

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Abstract

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, and UK Department of Health.

Original languageEnglish (US)
Pages (from-to)27-39
Number of pages13
JournalThe Lancet Oncology
Volume19
Issue number1
DOIs
StatePublished - Jan 1 2018

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Adjuvant Chemotherapy
Meta-Analysis
Breast Neoplasms
Drug Therapy
Recurrence
Neoplasms
Breast
Mortality
Therapeutics
Intention to Treat Analysis
Segmental Mastectomy
Anthracyclines
Biomedical Research
Cause of Death

ASJC Scopus subject areas

  • Oncology

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Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer : meta-analysis of individual patient data from ten randomised trials. / Early Breast Cancer Trialists' Collaborative Group (EBCTCG).

In: The Lancet Oncology, Vol. 19, No. 1, 01.01.2018, p. 27-39.

Research output: Contribution to journalArticle

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title = "Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials",
abstract = "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, and UK Department of Health.",
author = "{Early Breast Cancer Trialists' Collaborative Group (EBCTCG)} and Bernard Asselain and William Barlow and John Bartlett and Jonas Bergh and Elizabeth Bergsten-Nordstr{\"o}m and Judith Bliss and Francesco Boccardo and Clare Boddington and Jan Bogaerts and Gianni Bonadonna and Rosie Bradley and Etienne Brain and Jeremy Braybrooke and Philippe Broet and John Bryant and Julie Burrett and David Cameron and Mike Clarke and Alan Coates and Robert Coleman and Coombes, {Raoul Charles} and Candace Correa and Joe Costantino and Jack Cuzick and David Danforth and Nancy Davidson and Christina Davies and Lucy Davies and {Di Leo}, Angelo and David Dodwell and Mitch Dowsett and Fran Duane and Vaughan Evans and Marianne Ewertz and Bernard Fisher and John Forbes and Leslie Ford and Gazet, {Jean Claude} and Richard Gelber and Lucy Gettins and Luca Gianni and Michael Gnant and Jon Godwin and Aron Goldhirsch and Pamela Goodwin and Richard Gray and Daniel Hayes and Catherine Hill and James Ingle and Reshma Jagsi",
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month = "1",
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doi = "10.1016/S1470-2045(17)30777-5",
language = "English (US)",
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pages = "27--39",
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TY - JOUR

T1 - Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer

T2 - meta-analysis of individual patient data from ten randomised trials

AU - Early Breast Cancer Trialists' Collaborative Group (EBCTCG)

AU - Asselain, Bernard

AU - Barlow, William

AU - Bartlett, John

AU - Bergh, Jonas

AU - Bergsten-Nordström, Elizabeth

AU - Bliss, Judith

AU - Boccardo, Francesco

AU - Boddington, Clare

AU - Bogaerts, Jan

AU - Bonadonna, Gianni

AU - Bradley, Rosie

AU - Brain, Etienne

AU - Braybrooke, Jeremy

AU - Broet, Philippe

AU - Bryant, John

AU - Burrett, Julie

AU - Cameron, David

AU - Clarke, Mike

AU - Coates, Alan

AU - Coleman, Robert

AU - Coombes, Raoul Charles

AU - Correa, Candace

AU - Costantino, Joe

AU - Cuzick, Jack

AU - Danforth, David

AU - Davidson, Nancy

AU - Davies, Christina

AU - Davies, Lucy

AU - Di Leo, Angelo

AU - Dodwell, David

AU - Dowsett, Mitch

AU - Duane, Fran

AU - Evans, Vaughan

AU - Ewertz, Marianne

AU - Fisher, Bernard

AU - Forbes, John

AU - Ford, Leslie

AU - Gazet, Jean Claude

AU - Gelber, Richard

AU - Gettins, Lucy

AU - Gianni, Luca

AU - Gnant, Michael

AU - Godwin, Jon

AU - Goldhirsch, Aron

AU - Goodwin, Pamela

AU - Gray, Richard

AU - Hayes, Daniel

AU - Hill, Catherine

AU - Ingle, James

AU - Jagsi, Reshma

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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, and UK Department of Health.

AB - 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, and UK Department of Health.

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