TY - JOUR
T1 - Radiotherapy to regional nodes in early breast cancer
T2 - an individual patient data meta-analysis of 14 324 women in 16 trials
AU - Early Breast Cancer Trialists’ Collaborative Group (EBCTCG)
AU - Taylor, Carolyn
AU - Dodwell, David
AU - McGale, Paul
AU - Hills, Robert K.
AU - Berry, Richard
AU - Bradley, Rosie
AU - Braybrooke, Jeremy
AU - Clarke, Mike
AU - Gray, Richard
AU - Holt, Francesca
AU - Liu, Zulian
AU - Pan, Hongchao
AU - Peto, Richard
AU - Straiton, Ewan
AU - Coles, Charlotte
AU - Duane, Fran
AU - Hennequin, Christophe
AU - Jones, Glenn
AU - Kühn, Thorsten
AU - Oliveros, Sileida
AU - Overgaard, Jens
AU - Pritchard, Kathy I.
AU - Suh, Chang Ok
AU - Beake, Graham
AU - Boddington, Clare
AU - Davies, Christina
AU - Davies, Lucy
AU - Evans, Vaughan
AU - Gay, Jo
AU - Gettins, Lucy
AU - Godwin, Jon
AU - James, Sam
AU - Kerr, Amanda
AU - Liu, Hui
AU - MacKinnon, Elizabeth
AU - Mannu, Gurdeep
AU - McHugh, Theresa
AU - Morris, Philip
AU - Nakahara, Mariko
AU - Read, Simon
AU - Taylor, Hannah
AU - Ferguson, John
AU - Scheurlen, Hans
AU - Zurrida, Stefano
AU - Galimberti, Viviana
AU - Ingle, James
AU - Valagussa, Pinuccia
AU - Veronesi, Umberto
AU - Anderson, Stewart
AU - Goetz, Matthew
N1 - Publisher Copyright:
© 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2023/11/25
Y1 - 2023/11/25
N2 - Background: Radiotherapy has become much better targeted since the 1980s, improving both safety and efficacy. In breast cancer, radiotherapy to regional lymph nodes aims to reduce risks of recurrence and death. Its effects have been studied in randomised trials, some before the 1980s and some after. We aimed to assess the effects of regional node radiotherapy in these two eras. Methods: In this meta-analysis of individual patient data, we sought data from all randomised trials of regional lymph node radiotherapy versus no regional lymph node radiotherapy in women with early breast cancer (including one study that irradiated lymph nodes only if the cancer was right-sided). Trials were identified through the EBCTCG's regular systematic searches of databases including MEDLINE, Embase, the Cochrane Library, and meeting abstracts. Trials were eligible if they began before Jan 1, 2009. The only systematic difference between treatment groups was in regional node radiotherapy (to the internal mammary chain, supraclavicular fossa, or axilla, or any combinations of these). Primary outcomes were recurrence at any site, breast cancer mortality, non-breast-cancer mortality, and all-cause mortality. Data were supplied by trialists and standardised into a format suitable for analysis. A summary of the formatted data was returned to trialists for verification. Log-rank analyses yielded first-event rate ratios (RRs) and confidence intervals. Findings: We found 17 eligible trials, 16 of which had available data (for 14 324 participants), and one of which (henceforth excluded), had unavailable data (for 165 participants). In the eight newer trials (12 167 patients), which started during 1989–2008, regional node radiotherapy significantly reduced recurrence (rate ratio 0·88, 95% CI 0·81–0·95; p=0·0008). The main effect was on distant recurrence as few regional node recurrences were reported. Radiotherapy significantly reduced breast cancer mortality (RR 0·87, 95% CI 0·80–0·94; p=0·0010), with no significant effect on non-breast-cancer mortality (0·97, 0·84–1·11; p=0·63), leading to significantly reduced all-cause mortality (0·90, 0·84–0·96; p=0·0022). In an illustrative calculation, estimated absolute reductions in 15-year breast cancer mortality were 1·6% for women with no positive axillary nodes, 2·7% for those with one to three positive axillary nodes, and 4·5% for those with four or more positive axillary nodes. In the eight older trials (2157 patients), which started during 1961–78, regional node radiotherapy had little effect on breast cancer mortality (RR 1·04, 95% CI 0·91–1·20; p=0·55), but significantly increased non-breast-cancer mortality (1·42, 1·18–1·71; p=0·00023), with risk mainly after year 20, and all-cause mortality (1·17, 1·04–1·31; p=0·0067). Interpretation: Regional node radiotherapy significantly reduced breast cancer mortality and all-cause mortality in trials done after the 1980s, but not in older trials. These contrasting findings could reflect radiotherapy improvements since the 1980s. Funding: Cancer Research UK, Medical Research Council.
AB - Background: Radiotherapy has become much better targeted since the 1980s, improving both safety and efficacy. In breast cancer, radiotherapy to regional lymph nodes aims to reduce risks of recurrence and death. Its effects have been studied in randomised trials, some before the 1980s and some after. We aimed to assess the effects of regional node radiotherapy in these two eras. Methods: In this meta-analysis of individual patient data, we sought data from all randomised trials of regional lymph node radiotherapy versus no regional lymph node radiotherapy in women with early breast cancer (including one study that irradiated lymph nodes only if the cancer was right-sided). Trials were identified through the EBCTCG's regular systematic searches of databases including MEDLINE, Embase, the Cochrane Library, and meeting abstracts. Trials were eligible if they began before Jan 1, 2009. The only systematic difference between treatment groups was in regional node radiotherapy (to the internal mammary chain, supraclavicular fossa, or axilla, or any combinations of these). Primary outcomes were recurrence at any site, breast cancer mortality, non-breast-cancer mortality, and all-cause mortality. Data were supplied by trialists and standardised into a format suitable for analysis. A summary of the formatted data was returned to trialists for verification. Log-rank analyses yielded first-event rate ratios (RRs) and confidence intervals. Findings: We found 17 eligible trials, 16 of which had available data (for 14 324 participants), and one of which (henceforth excluded), had unavailable data (for 165 participants). In the eight newer trials (12 167 patients), which started during 1989–2008, regional node radiotherapy significantly reduced recurrence (rate ratio 0·88, 95% CI 0·81–0·95; p=0·0008). The main effect was on distant recurrence as few regional node recurrences were reported. Radiotherapy significantly reduced breast cancer mortality (RR 0·87, 95% CI 0·80–0·94; p=0·0010), with no significant effect on non-breast-cancer mortality (0·97, 0·84–1·11; p=0·63), leading to significantly reduced all-cause mortality (0·90, 0·84–0·96; p=0·0022). In an illustrative calculation, estimated absolute reductions in 15-year breast cancer mortality were 1·6% for women with no positive axillary nodes, 2·7% for those with one to three positive axillary nodes, and 4·5% for those with four or more positive axillary nodes. In the eight older trials (2157 patients), which started during 1961–78, regional node radiotherapy had little effect on breast cancer mortality (RR 1·04, 95% CI 0·91–1·20; p=0·55), but significantly increased non-breast-cancer mortality (1·42, 1·18–1·71; p=0·00023), with risk mainly after year 20, and all-cause mortality (1·17, 1·04–1·31; p=0·0067). Interpretation: Regional node radiotherapy significantly reduced breast cancer mortality and all-cause mortality in trials done after the 1980s, but not in older trials. These contrasting findings could reflect radiotherapy improvements since the 1980s. Funding: Cancer Research UK, Medical Research Council.
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U2 - 10.1016/S0140-6736(23)01082-6
DO - 10.1016/S0140-6736(23)01082-6
M3 - Article
C2 - 37931633
AN - SCOPUS:85177975667
SN - 0140-6736
VL - 402
SP - 1991
EP - 2003
JO - The Lancet
JF - The Lancet
IS - 10416
ER -