Wide‐field radiation as adjunct to adjuvant chemotherapy in high‐risk cases with early breast cancer: Do it or not?

Abstract

Very few developments in the management of human malignancies have been as controversial as the role of locoregional (wide-field) radiotherapy (RT) in the adjuvant therapy of early breast cancer. This is mostly due to the fact that older trials using more obsolete radiation equipment and treatment planning, while showing a significant reduction of locoregional recurrences, indicated only a moderate improvement of systemic metastases. Also, because of cardiac toxicity, increased cardiovascular mortality counteracted the modest benefits on breast cancer mortality, resulting in no significant changes in overall survival (EBCTCG, 1995;Cuzick et al., 1994).The most recent Oxford EBCTCG metanalysis indicates in its recent update a more substantial breast cancer mortality reduction (p ϭ 0.0001), but because of increased non-breast cancer mortality, particularly evident in trials started before 1975, the overall survival was improved only marginally (37.1% vs. 35.9%, p ϭ 0.06). Editorial comments towards this latest development are provided at the end of this review.With improved radiation technology and radiation planning and with the introduction of systemic therapies, the results of radiation are changing. At least 4 large randomized trials using relatively modern RT equipment reported a benefit of locoregional RT in terms of significant reductions in systemic recurrence and breast cancer mortality (Arriagada et al., 1995;Overgaard et al., 1997Overgaard et al., , 1999Ragaz et al., 1997). Also, a meta-analysis of more recent RT trials restricted to those with systemic therapy showed a significant mortality reduction due to radiation (Whelan et al., 2000). Thus, these studies confirm that modern RT does have a potential to substantially improve the survival outcome in high-risk breast cancer subsets.The most recent randomized trial published in the May issue of this Journal is the German study of Schmoor et al. Between 1984 -1989, one hundred and ninety nine node-positive breast cancer treated with adjuvant CMF chemotherapy were randomized, after a modified radical mastectomy, into CMFϩRT versus CMF alone. This study therefore represents a "modern" radiation trial. As this is the last of the recent trials reported in a peer review literature, several comments will be provided to bring this trial into perspective with the four better-known larger trials and with the Oxford Overview, and to clarify its contribution to the recent radiation literature. THE TRIAL OF SCHMOOR ET AL.At a median follow-up, the study of Schmoor et al. showed a significant reduction in locoregional recurrences [relative risk (RR) ϭ 0.35]. Also improved in RT patients were survival free of distant failure (RR ϭ 0.8) and breast cancer-specific survival (RR ϭ 0.79), but these improvements were not statistically significant. There was an increase in patients from the RT arm of non-breast cancer-related events (second malignancy, non-cancerrelated deaths). Thus, while breast cancer mortality was reduced by 21%, overall mortality was reduced only marg...