Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: Meta-analysis of individual patient data for 8135 women in 22 randomised trials

P. McGale, C. Taylor, C. Correa, D. Cutter, F. Duane, M. Ewertz, R. Gray, G. Mannu, R. Peto, T. Whelan, Y. Wang, Z. Wang, S. Darby, K. Albain, S. Anderson, R. Arriagada, W. Barlow, J. Bergh, E. Bergsten Nordström, J. BlissJ. A. Burrett, M. Buyse, D. Cameron, E. Carrasco, M. Clarke, R. Coleman, C. Correa, A. Coates, R. Collins, J. Costantino, D. Cutter, J. Cuzick, S. Darby, N. Davidson, C. Davies, K. Davies, A. Delmestri, A. Di Leo, M. Dowsett, P. Elphinstone, V. Evans, M. Ewertz, J. Forbes, R. Gelber, L. Gettins, C. Geyer, L. Gianni, M. Gnant, A. Goldhirsch, J. Godwin, R. Gray, C. Gregory, D. Hayes, C. Hill, J. Ingle, R. Jakesz, S. James, W. Janni, M. Kaufmann, A. Kerr, H. Liu, E. MacKinnon, M. Martín, P. McGale, T. McHugh, P. Morris, L. Norton, Y. Ohashi, S. Paik, H. C. Pan, E. Perez, R. Peto, M. Piccart, L. Pierce, K. Pritchard, G. Pruneri, V. Raina, P. Ravdin, J. Robertson, E. Rutgers, Y. F. Shao, J. Sparano, S. Swain, C. Taylor, P. Valagussa, G. Viale, G. Von Minckwitz, T. Whelan, E. Winer, X. Wiang, Y. Wang, W. Wood

Research output: Contribution to journalArticle

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Abstract

Background Postmastectomy radiotherapy was shown in previous meta-analyses to reduce the risks of both recurrence and breast cancer mortality in all women with node-positive disease considered together. However, the benefit in women with only one to three positive lymph nodes is uncertain. We aimed to assess the effect of radiotherapy in these women after mastectomy and axillary dissection. Methods We did a meta-analysis of individual data for 8135 women randomly assigned to treatment groups during 1964-86 in 22 trials of radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery versus the same surgery but no radiotherapy. Follow-up lasted 10 years for recurrence and to Jan 1, 2009, for mortality. Analyses were stratified by trial, individual follow-up year, age at entry, and pathological nodal status. Findings 3786 women had axillary dissection to at least level II and had zero, one to three, or four or more positive nodes. All were in trials in which radiotherapy included the chest wall, supraclavicular or axillary fossa (or both), and internal mammary chain. For 700 women with axillary dissection and no positive nodes, radiotherapy had no significant effect on locoregional recurrence (two-sided significance level [2p]>0·1), overall recurrence (rate ratio [RR], irradiated vs not, 1·06, 95% CI 0·76-1·48, 2p>0·1), or breast cancer mortality (RR 1·18, 95% CI 0·89-1·55, 2p>0·1). For 1314 women with axillary dissection and one to three positive nodes, radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·68, 95% CI 0·57-0·82, 2p=0·00006), and breast cancer mortality (RR 0·80, 95% CI 0·67-0·95, 2p=0·01). 1133 of these 1314 women were in trials in which systemic therapy (cyclophosphamide, methotrexate, and fl uorouracil, or tamoxifen) was given in both trial groups and, for them, radiotherapy again reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·67, 95% CI 0·55-0·82, 2p=0·00009), and breast cancer mortality (RR 0·78, 95% CI 0·64-0·94, 2p=0·01). For 1772 women with axillary dissection and four or more positive nodes, radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·79, 95% CI 0·69-0·90, 2p=0·0003), and breast cancer mortality (RR 0·87, 95% CI 0·77-0·99, 2p=0·04). Interpretation After mastectomy and axillary dissection, radiotherapy reduced both recurrence and breast cancer mortality in the women with one to three positive lymph nodes in these trials even when systemic therapy was given. For today's women, who in many countries are at lower risk of recurrence, absolute gains might be smaller but proportional gains might be larger because of more effective radiotherapy.

Original languageEnglish (US)
Pages (from-to)2127-2135
Number of pages9
JournalThe Lancet
Volume383
Issue number9935
DOIs
StatePublished - 2014

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Mastectomy
Meta-Analysis
Radiotherapy
Breast Neoplasms
Recurrence
Mortality
Dissection
Lymph Nodes
Thoracic Wall
Tamoxifen
Methotrexate
Cyclophosphamide
Breast
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

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Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality : Meta-analysis of individual patient data for 8135 women in 22 randomised trials. / McGale, P.; Taylor, C.; Correa, C.; Cutter, D.; Duane, F.; Ewertz, M.; Gray, R.; Mannu, G.; Peto, R.; Whelan, T.; Wang, Y.; Wang, Z.; Darby, S.; Albain, K.; Anderson, S.; Arriagada, R.; Barlow, W.; Bergh, J.; Bergsten Nordström, E.; Bliss, J.; Burrett, J. A.; Buyse, M.; Cameron, D.; Carrasco, E.; Clarke, M.; Coleman, R.; Correa, C.; Coates, A.; Collins, R.; Costantino, J.; Cutter, D.; Cuzick, J.; Darby, S.; Davidson, N.; Davies, C.; Davies, K.; Delmestri, A.; Di Leo, A.; Dowsett, M.; Elphinstone, P.; Evans, V.; Ewertz, M.; Forbes, J.; Gelber, R.; Gettins, L.; Geyer, C.; Gianni, L.; Gnant, M.; Goldhirsch, A.; Godwin, J.; Gray, R.; Gregory, C.; Hayes, D.; Hill, C.; Ingle, J.; Jakesz, R.; James, S.; Janni, W.; Kaufmann, M.; Kerr, A.; Liu, H.; MacKinnon, E.; Martín, M.; McGale, P.; McHugh, T.; Morris, P.; Norton, L.; Ohashi, Y.; Paik, S.; Pan, H. C.; Perez, E.; Peto, R.; Piccart, M.; Pierce, L.; Pritchard, K.; Pruneri, G.; Raina, V.; Ravdin, P.; Robertson, J.; Rutgers, E.; Shao, Y. F.; Sparano, J.; Swain, S.; Taylor, C.; Valagussa, P.; Viale, G.; Von Minckwitz, G.; Whelan, T.; Winer, E.; Wiang, X.; Wang, Y.; Wood, W.

In: The Lancet, Vol. 383, No. 9935, 2014, p. 2127-2135.

Research output: Contribution to journalArticle

McGale, P, Taylor, C, Correa, C, Cutter, D, Duane, F, Ewertz, M, Gray, R, Mannu, G, Peto, R, Whelan, T, Wang, Y, Wang, Z, Darby, S, Albain, K, Anderson, S, Arriagada, R, Barlow, W, Bergh, J, Bergsten Nordström, E, Bliss, J, Burrett, JA, Buyse, M, Cameron, D, Carrasco, E, Clarke, M, Coleman, R, Correa, C, Coates, A, Collins, R, Costantino, J, Cutter, D, Cuzick, J, Darby, S, Davidson, N, Davies, C, Davies, K, Delmestri, A, Di Leo, A, Dowsett, M, Elphinstone, P, Evans, V, Ewertz, M, Forbes, J, Gelber, R, Gettins, L, Geyer, C, Gianni, L, Gnant, M, Goldhirsch, A, Godwin, J, Gray, R, Gregory, C, Hayes, D, Hill, C, Ingle, J, Jakesz, R, James, S, Janni, W, Kaufmann, M, Kerr, A, Liu, H, MacKinnon, E, Martín, M, McGale, P, McHugh, T, Morris, P, Norton, L, Ohashi, Y, Paik, S, Pan, HC, Perez, E, Peto, R, Piccart, M, Pierce, L, Pritchard, K, Pruneri, G, Raina, V, Ravdin, P, Robertson, J, Rutgers, E, Shao, YF, Sparano, J, Swain, S, Taylor, C, Valagussa, P, Viale, G, Von Minckwitz, G, Whelan, T, Winer, E, Wiang, X, Wang, Y & Wood, W 2014, 'Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: Meta-analysis of individual patient data for 8135 women in 22 randomised trials', The Lancet, vol. 383, no. 9935, pp. 2127-2135. https://doi.org/10.1016/S0140-6736(14)60488-8
McGale, P. ; Taylor, C. ; Correa, C. ; Cutter, D. ; Duane, F. ; Ewertz, M. ; Gray, R. ; Mannu, G. ; Peto, R. ; Whelan, T. ; Wang, Y. ; Wang, Z. ; Darby, S. ; Albain, K. ; Anderson, S. ; Arriagada, R. ; Barlow, W. ; Bergh, J. ; Bergsten Nordström, E. ; Bliss, J. ; Burrett, J. A. ; Buyse, M. ; Cameron, D. ; Carrasco, E. ; Clarke, M. ; Coleman, R. ; Correa, C. ; Coates, A. ; Collins, R. ; Costantino, J. ; Cutter, D. ; Cuzick, J. ; Darby, S. ; Davidson, N. ; Davies, C. ; Davies, K. ; Delmestri, A. ; Di Leo, A. ; Dowsett, M. ; Elphinstone, P. ; Evans, V. ; Ewertz, M. ; Forbes, J. ; Gelber, R. ; Gettins, L. ; Geyer, C. ; Gianni, L. ; Gnant, M. ; Goldhirsch, A. ; Godwin, J. ; Gray, R. ; Gregory, C. ; Hayes, D. ; Hill, C. ; Ingle, J. ; Jakesz, R. ; James, S. ; Janni, W. ; Kaufmann, M. ; Kerr, A. ; Liu, H. ; MacKinnon, E. ; Martín, M. ; McGale, P. ; McHugh, T. ; Morris, P. ; Norton, L. ; Ohashi, Y. ; Paik, S. ; Pan, H. C. ; Perez, E. ; Peto, R. ; Piccart, M. ; Pierce, L. ; Pritchard, K. ; Pruneri, G. ; Raina, V. ; Ravdin, P. ; Robertson, J. ; Rutgers, E. ; Shao, Y. F. ; Sparano, J. ; Swain, S. ; Taylor, C. ; Valagussa, P. ; Viale, G. ; Von Minckwitz, G. ; Whelan, T. ; Winer, E. ; Wiang, X. ; Wang, Y. ; Wood, W. / Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality : Meta-analysis of individual patient data for 8135 women in 22 randomised trials. In: The Lancet. 2014 ; Vol. 383, No. 9935. pp. 2127-2135.
@article{526e5bde07a74f5dafeb23dab260789d,
title = "Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: Meta-analysis of individual patient data for 8135 women in 22 randomised trials",
abstract = "Background Postmastectomy radiotherapy was shown in previous meta-analyses to reduce the risks of both recurrence and breast cancer mortality in all women with node-positive disease considered together. However, the benefit in women with only one to three positive lymph nodes is uncertain. We aimed to assess the effect of radiotherapy in these women after mastectomy and axillary dissection. Methods We did a meta-analysis of individual data for 8135 women randomly assigned to treatment groups during 1964-86 in 22 trials of radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery versus the same surgery but no radiotherapy. Follow-up lasted 10 years for recurrence and to Jan 1, 2009, for mortality. Analyses were stratified by trial, individual follow-up year, age at entry, and pathological nodal status. Findings 3786 women had axillary dissection to at least level II and had zero, one to three, or four or more positive nodes. All were in trials in which radiotherapy included the chest wall, supraclavicular or axillary fossa (or both), and internal mammary chain. For 700 women with axillary dissection and no positive nodes, radiotherapy had no significant effect on locoregional recurrence (two-sided significance level [2p]>0·1), overall recurrence (rate ratio [RR], irradiated vs not, 1·06, 95{\%} CI 0·76-1·48, 2p>0·1), or breast cancer mortality (RR 1·18, 95{\%} CI 0·89-1·55, 2p>0·1). For 1314 women with axillary dissection and one to three positive nodes, radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·68, 95{\%} CI 0·57-0·82, 2p=0·00006), and breast cancer mortality (RR 0·80, 95{\%} CI 0·67-0·95, 2p=0·01). 1133 of these 1314 women were in trials in which systemic therapy (cyclophosphamide, methotrexate, and fl uorouracil, or tamoxifen) was given in both trial groups and, for them, radiotherapy again reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·67, 95{\%} CI 0·55-0·82, 2p=0·00009), and breast cancer mortality (RR 0·78, 95{\%} CI 0·64-0·94, 2p=0·01). For 1772 women with axillary dissection and four or more positive nodes, radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·79, 95{\%} CI 0·69-0·90, 2p=0·0003), and breast cancer mortality (RR 0·87, 95{\%} CI 0·77-0·99, 2p=0·04). Interpretation After mastectomy and axillary dissection, radiotherapy reduced both recurrence and breast cancer mortality in the women with one to three positive lymph nodes in these trials even when systemic therapy was given. For today's women, who in many countries are at lower risk of recurrence, absolute gains might be smaller but proportional gains might be larger because of more effective radiotherapy.",
author = "P. McGale and C. Taylor and C. Correa and D. Cutter and F. Duane and M. Ewertz and R. Gray and G. Mannu and R. Peto and T. Whelan and Y. Wang and Z. Wang and S. Darby and K. Albain and S. Anderson and R. Arriagada and W. Barlow and J. Bergh and {Bergsten Nordstr{\"o}m}, E. and J. Bliss and Burrett, {J. A.} and M. Buyse and D. Cameron and E. Carrasco and M. Clarke and R. Coleman and C. Correa and A. Coates and R. Collins and J. Costantino and D. Cutter and J. Cuzick and S. Darby and N. Davidson and C. Davies and K. Davies and A. Delmestri and {Di Leo}, A. and M. Dowsett and P. Elphinstone and V. Evans and M. Ewertz and J. Forbes and R. Gelber and L. Gettins and C. Geyer and L. Gianni and M. Gnant and A. Goldhirsch and J. Godwin and R. Gray and C. Gregory and D. Hayes and C. Hill and J. Ingle and R. Jakesz and S. James and W. Janni and M. Kaufmann and A. Kerr and H. Liu and E. MacKinnon and M. Mart{\'i}n and P. McGale and T. McHugh and P. Morris and L. Norton and Y. Ohashi and S. Paik and Pan, {H. C.} and E. Perez and R. Peto and M. Piccart and L. Pierce and K. Pritchard and G. Pruneri and V. Raina and P. Ravdin and J. Robertson and E. Rutgers and Shao, {Y. F.} and J. Sparano and S. Swain and C. Taylor and P. Valagussa and G. Viale and {Von Minckwitz}, G. and T. Whelan and E. Winer and X. Wiang and Y. Wang and W. Wood",
year = "2014",
doi = "10.1016/S0140-6736(14)60488-8",
language = "English (US)",
volume = "383",
pages = "2127--2135",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",
number = "9935",

}

TY - JOUR

T1 - Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality

T2 - Meta-analysis of individual patient data for 8135 women in 22 randomised trials

AU - McGale, P.

AU - Taylor, C.

AU - Correa, C.

AU - Cutter, D.

AU - Duane, F.

AU - Ewertz, M.

AU - Gray, R.

AU - Mannu, G.

AU - Peto, R.

AU - Whelan, T.

AU - Wang, Y.

AU - Wang, Z.

AU - Darby, S.

AU - Albain, K.

AU - Anderson, S.

AU - Arriagada, R.

AU - Barlow, W.

AU - Bergh, J.

AU - Bergsten Nordström, E.

AU - Bliss, J.

AU - Burrett, J. A.

AU - Buyse, M.

AU - Cameron, D.

AU - Carrasco, E.

AU - Clarke, M.

AU - Coleman, R.

AU - Correa, C.

AU - Coates, A.

AU - Collins, R.

AU - Costantino, J.

AU - Cutter, D.

AU - Cuzick, J.

AU - Darby, S.

AU - Davidson, N.

AU - Davies, C.

AU - Davies, K.

AU - Delmestri, A.

AU - Di Leo, A.

AU - Dowsett, M.

AU - Elphinstone, P.

AU - Evans, V.

AU - Ewertz, M.

AU - Forbes, J.

AU - Gelber, R.

AU - Gettins, L.

AU - Geyer, C.

AU - Gianni, L.

AU - Gnant, M.

AU - Goldhirsch, A.

AU - Godwin, J.

AU - Gray, R.

AU - Gregory, C.

AU - Hayes, D.

AU - Hill, C.

AU - Ingle, J.

AU - Jakesz, R.

AU - James, S.

AU - Janni, W.

AU - Kaufmann, M.

AU - Kerr, A.

AU - Liu, H.

AU - MacKinnon, E.

AU - Martín, M.

AU - McGale, P.

AU - McHugh, T.

AU - Morris, P.

AU - Norton, L.

AU - Ohashi, Y.

AU - Paik, S.

AU - Pan, H. C.

AU - Perez, E.

AU - Peto, R.

AU - Piccart, M.

AU - Pierce, L.

AU - Pritchard, K.

AU - Pruneri, G.

AU - Raina, V.

AU - Ravdin, P.

AU - Robertson, J.

AU - Rutgers, E.

AU - Shao, Y. F.

AU - Sparano, J.

AU - Swain, S.

AU - Taylor, C.

AU - Valagussa, P.

AU - Viale, G.

AU - Von Minckwitz, G.

AU - Whelan, T.

AU - Winer, E.

AU - Wiang, X.

AU - Wang, Y.

AU - Wood, W.

PY - 2014

Y1 - 2014

N2 - Background Postmastectomy radiotherapy was shown in previous meta-analyses to reduce the risks of both recurrence and breast cancer mortality in all women with node-positive disease considered together. However, the benefit in women with only one to three positive lymph nodes is uncertain. We aimed to assess the effect of radiotherapy in these women after mastectomy and axillary dissection. Methods We did a meta-analysis of individual data for 8135 women randomly assigned to treatment groups during 1964-86 in 22 trials of radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery versus the same surgery but no radiotherapy. Follow-up lasted 10 years for recurrence and to Jan 1, 2009, for mortality. Analyses were stratified by trial, individual follow-up year, age at entry, and pathological nodal status. Findings 3786 women had axillary dissection to at least level II and had zero, one to three, or four or more positive nodes. All were in trials in which radiotherapy included the chest wall, supraclavicular or axillary fossa (or both), and internal mammary chain. For 700 women with axillary dissection and no positive nodes, radiotherapy had no significant effect on locoregional recurrence (two-sided significance level [2p]>0·1), overall recurrence (rate ratio [RR], irradiated vs not, 1·06, 95% CI 0·76-1·48, 2p>0·1), or breast cancer mortality (RR 1·18, 95% CI 0·89-1·55, 2p>0·1). For 1314 women with axillary dissection and one to three positive nodes, radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·68, 95% CI 0·57-0·82, 2p=0·00006), and breast cancer mortality (RR 0·80, 95% CI 0·67-0·95, 2p=0·01). 1133 of these 1314 women were in trials in which systemic therapy (cyclophosphamide, methotrexate, and fl uorouracil, or tamoxifen) was given in both trial groups and, for them, radiotherapy again reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·67, 95% CI 0·55-0·82, 2p=0·00009), and breast cancer mortality (RR 0·78, 95% CI 0·64-0·94, 2p=0·01). For 1772 women with axillary dissection and four or more positive nodes, radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·79, 95% CI 0·69-0·90, 2p=0·0003), and breast cancer mortality (RR 0·87, 95% CI 0·77-0·99, 2p=0·04). Interpretation After mastectomy and axillary dissection, radiotherapy reduced both recurrence and breast cancer mortality in the women with one to three positive lymph nodes in these trials even when systemic therapy was given. For today's women, who in many countries are at lower risk of recurrence, absolute gains might be smaller but proportional gains might be larger because of more effective radiotherapy.

AB - Background Postmastectomy radiotherapy was shown in previous meta-analyses to reduce the risks of both recurrence and breast cancer mortality in all women with node-positive disease considered together. However, the benefit in women with only one to three positive lymph nodes is uncertain. We aimed to assess the effect of radiotherapy in these women after mastectomy and axillary dissection. Methods We did a meta-analysis of individual data for 8135 women randomly assigned to treatment groups during 1964-86 in 22 trials of radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery versus the same surgery but no radiotherapy. Follow-up lasted 10 years for recurrence and to Jan 1, 2009, for mortality. Analyses were stratified by trial, individual follow-up year, age at entry, and pathological nodal status. Findings 3786 women had axillary dissection to at least level II and had zero, one to three, or four or more positive nodes. All were in trials in which radiotherapy included the chest wall, supraclavicular or axillary fossa (or both), and internal mammary chain. For 700 women with axillary dissection and no positive nodes, radiotherapy had no significant effect on locoregional recurrence (two-sided significance level [2p]>0·1), overall recurrence (rate ratio [RR], irradiated vs not, 1·06, 95% CI 0·76-1·48, 2p>0·1), or breast cancer mortality (RR 1·18, 95% CI 0·89-1·55, 2p>0·1). For 1314 women with axillary dissection and one to three positive nodes, radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·68, 95% CI 0·57-0·82, 2p=0·00006), and breast cancer mortality (RR 0·80, 95% CI 0·67-0·95, 2p=0·01). 1133 of these 1314 women were in trials in which systemic therapy (cyclophosphamide, methotrexate, and fl uorouracil, or tamoxifen) was given in both trial groups and, for them, radiotherapy again reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·67, 95% CI 0·55-0·82, 2p=0·00009), and breast cancer mortality (RR 0·78, 95% CI 0·64-0·94, 2p=0·01). For 1772 women with axillary dissection and four or more positive nodes, radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·79, 95% CI 0·69-0·90, 2p=0·0003), and breast cancer mortality (RR 0·87, 95% CI 0·77-0·99, 2p=0·04). Interpretation After mastectomy and axillary dissection, radiotherapy reduced both recurrence and breast cancer mortality in the women with one to three positive lymph nodes in these trials even when systemic therapy was given. For today's women, who in many countries are at lower risk of recurrence, absolute gains might be smaller but proportional gains might be larger because of more effective radiotherapy.

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