Radiotherapy to regional nodes in early breast cancer: an individual patient data meta-analysis of 14 324 women in 16 trials
- PMID: 37931633
- DOI: 10.1016/S0140-6736(23)01082-6
Radiotherapy to regional nodes in early breast cancer: an individual patient data meta-analysis of 14 324 women in 16 trials
Abstract
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.
Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Declaration of interests RG and RKH report that EBCTCG is supported by a Cancer Research UK grant (reference 27691) paid to the University of Oxford. JBe reports institutional grants or contracts from Amgen, AstraZeneca, Bayer, Merck, Pfizer, Roche, and Sanofi-Aventis; honoraria from UpToDate to Asklepios Medicine for breast cancer prediction or prognostication for early beast cancer; has been offered stock options and stocks in Stratipath artificial intelligence for early breast cancer and was asked to arrange an international advisory board for Stratipath; has had a leadership or fiduciary role in other board, society, committee, or advocacy groups; and has a leadership or fiduciary role with the WNTRESEARCH Group (https://www.wntresearch.com) since June, 2022. CC reports institutional grants or contracts from: Radiation Research Network Project Seed Funding Award—Multi-modal Imaging-Guided Radiotherapy for small Animals with a Technological and Extensible System; Cancer Research UK (ref: RRNPSF-Jul21\100012); Addenbrooke's Charitable Trust fund 9701 (Tomlinson Radiotherapy legacy); The Lancet Breast Cancer Commission; Efficacy and Mechanism Evaluation Project (grant number: NIHR131120; Radiation Research Network Project Seed Funding Award for the Hamlet. RT multi-centre expansion (reference: RRNPSF-Jan21\100004), The National Institute for Health and Care Research (reference NIHR300024), and Cancer Research UK Radiation Research Unit at the University of Cambridge (reference C17918/A28870). CC reports the following board participation: Chair of Independent Data Monitoring Committee for UK PivotalBoost trial, Member of the independent data monitoring committee for TORPEdO Proton Beam Therapy trial; European HYPO-G01 breast fractionation trial; and the UK NIMRAD trial, and Member of International Scientific Advisory Board, Institute Curie. CC is a chair of The Lancet Breast Cancer Commission. KP reports royalty or license payments from UpToDate, and payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from Pfizer, Roche, Amgen, Novartis, Eisai, Genomic Health, and Myriad Genetic Laboratories; and payment for data safety monitoring board or advisory board participation from Pfizer and Gilead Sciences. SS reports grants or contracts from Genentec/Roche, Kailos Genetics, and Breast Cancer Research Fellowship; consulting fees from Genentech, Roche, and Molecular Therapeutics; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Genentech, Roche, and Daiichi Sankyo; support for attending meetings and travel from Genentech and Roche, and travel to Boston in November, 2019; participation on a data safety monitoring board for AstraZeneca; participation on an advisory board for AstraZeneca, Daiichi Sankyo, Exact Sciences, Biotheranostics, Natera, Merck, Silverback Therapeutics, and Athenex, Lilly; scientific advisory board participation for Inivata; leadership or fiduciary role in other board, society, committee, or advocacy group for NSABP as a vice chairman, Conquer Cancer Foundation, and American Society of Clinical Oncology Director; and writing services for third party writing for Genentech, Roche, and AstraZeneca. TW reports grants or contracts from Exact Sciences for In-Kind research funding, including non-direct financial support for biomarker testing from Exact Sciences for related and unrelated ongoing studies. All other authors declare no competing interests.
Comment in
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Effective and safe regional node irradiation in early breast cancer.Lancet. 2023 Nov 25;402(10416):1943-1945. doi: 10.1016/S0140-6736(23)01614-8. Epub 2023 Nov 3. Lancet. 2023. PMID: 37931630 No abstract available.
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