Adjuvant radiotherapy for breast cancer significantly improves overall survival: the missing link

Background and purpose: The influence of surgical adjuvant radiotherapy on overall survival of patients with operable breast cancer is still a controv ersial subject. The negative result of the EBCTCG meta-analysis (Early brea st cancer trialists', collaborative group. Effects of radiotherapy and surg ery in early breast cancer. An overview of the randomised trials, N. Engl, J. Med. 1995;333:1444-1455) of clinical randomized trials on adjuvant radio therapy in breast cancer is in strong contrast with the Danish 82B, 82C and British Columbia trials (Overgaard M, Hanse PS, Overgaar J, et al. Postope rative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N. Engl. J. Med. 1997:337:949-955; Overgaard M, Jensen MB, Overgaard J, et al. Postoperative radiotherapy in high-risk postmenopausal breast-ca ncer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Gr oup DBCG 82c randomized trial. Lancet 1999:353:1641-1648; Ragaz J, Jackson S, Le N, et al. Adjuvant radiotherapy and chemotherapy in node-positive pre menopausal women with breast cancer. N. Engl. J. Med. 1997;337:956-962) sho wing an impressive survival benefit. This paper tries to fill in the gap be tween the conflicting results. Materials and methods: The 36 trials of the EBCTCG (Early breast cancer tri alists', collaborative group, 1995) were prospectively screened for a numbe r of objective parameters that are usually not analyzed in review papers. T he odds of death data (and its variance) were borrowed from the original me ta-analysis (Early breast cancer trialists', collaborative group, 1995) to check whether the objective features were significant predictors for overal l survival benefit. Results: A significant survival benefit for the radiotherapy arm was found for recent trials (2P < 0.05), large trials (2P < 0.03), trials that used s tandard fractionation (2P < 0.02), and trials with a favourable crude survi val (2P < 0.03). For these four parameters clear parameter effect relations were found. In recent and large trials the odds reduction was 12.4% (2P = 0.004). Conclusions: Surgical adjuvant radiotherapy significantly improves overall survival of breast cancer patients provided that current techniques are use d and treatment is given with standard fractionation. For the best subgroup s we observed an odds of death reduction of more than 20%. The results of t his study stress the importance of reducing cardiovascular and other late t oxicity in adjuvant radiotherapy for breast cancer. (C) 2000 Elsevier Scien ce Ireland Ltd. All rights reserved.