Radiotherapy to regional nodes in early breast cancer: an individual patient data meta-analysis of 14 324 women in 16 trials

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 center dot 88, 95% CI 0 center dot 81-0 center dot 95; p=0 center dot 0008). The main effect was on distant recurrence as few regional node recurrences were reported. Radiotherapy significantly reduced breast cancer mortality (RR 0 center dot 87, 95% CI 0 center dot 80-0 center dot 94; p=0 center dot 0010), with no significant effect on non-breast-cancer mortality (0 center dot 97, 0 center dot 84-1 center dot 11; p=0 center dot 63), leading to significantly reduced all-cause mortality (0 center dot 90, 0 center dot 84-0 center dot 96; p=0 center dot 0022). In an illustrative calculation, estimated absolute reductions in 15-year breast cancer mortality were 1 center dot 6% for women with no positive axillary nodes, 2 center dot 7% for those with one to three positive axillary nodes, and 4 center dot 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 center dot 04, 95% CI 0 center dot 91-1 center dot 20; p=0 center dot 55), but significantly increased non-breast-cancer mortality (1 center dot 42, 1 center dot 18-1 center dot 71; p=0 center dot 00023), with risk mainly after year 20, and all-cause mortality (1 center dot 17, 1 center dot 04-1 center dot 31; p=0 center dot 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