Radiotherapy is often given after breast-conserving surgery for early breast cancer (eBC) with the aim of reducing the risk of recurrence and death. This meta-analysis compared data from randomised trials using regional and no-regional lymph node radiotherapy in women with eBC and showed that regional node radiotherapy significantly reduced BC mortality and all-cause mortality in trials done after the 1980s, but not in older trials, probably reflecting radiotherapy improvements in the last decades.
Following breast-conserving surgery (BCS) or mastectomy for node-positive disease, postoperative radiotherapy can reduce breast cancer (BC) mortality. Radiotherapy can be delivered not only to the breast or chest wall but also to the regional lymph nodes. The landscape of regional node radiotherapy has undergone significant transformations over the decades. In the 1960s and 1970s, radiotherapy typically involved photon beams that often irradiated the heart and lungs. In the 1980s and 1990s, these techniques were replaced by more tailored methods that involved much lower exposure of the heart and lungs, and more uniform coverage of target regions. This meta-analysis aimed to assess the effects of regional node radiotherapy on BC recurrence and mortality, reporting separate meta-analyses of the newer (1989–2008) and older trials (1961–78).
Methods
This meta-analysis compared data from randomised trials of regional lymph node radiotherapy vs. no regional lymph node radiotherapy in women with eBC. These 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, BC mortality, non-BC mortality, and all-cause mortality.
Study findings
In total, seventeen trials were eligible, of which sixteen had available data (n=14,324 participants). In the eight newer trials (12,167 patients), which started during 1989-2008, regional node radiotherapy significantly reduced recurrence (rate ratio (RR): 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 BC mortality (RR 0.87, 95%CI: 0.80-0.94; p=0.0010), with no significant effect on non-BC mortality (RR: 0.97, 95%CI: 0.84–1.11; p=0·63), leading to significantly reduced all-cause mortality (RR: 0.90, 95%CI: 0.84-0.96; p=0.0022). Estimated absolute reductions in 15-year BC 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 (2,157 patients), which started during 1961-78, regional node radiotherapy did not reduce overall BC recurrence (RR: 0.98, 95%CI: 0.85-1.12; p=0.74) or BC mortality (RR: 1.04, 95%CI: 0.91–1.20; p=0.55). Regional node radiotherapy significantly increased non-BC mortality (RR: 1.42, 95%CI: 1.18-1.71; p=0.00023), with little effect during the first 15 years, but a substantial excess thereafter, leading to a net increase in overall mortality (RR: 1.17, 95%CI: 1.04-1.31; p=0.0067).
In conclusion, regional node radiotherapy significantly reduced BC 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.
Reference
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