Correspondence
Radiotherapy and Surgery in Early Breast Cancer
N Engl J Med 1996; 334:989April 11, 1996
- Article
To the Editor:
I wish to propose some alternative ways to group patients and trials in the analysis of radiotherapy and surgery in early breast cancer, reported by the Early Breast Cancer Trialists' Collaborative Group (Nov. 30 issue).1
The studies included in Figure 1 and Figure 3 of the article used widely varying surgical and radiotherapeutic techniques. In a prior overview, single-agent and multiagent chemotherapeutic regimens and different periods of tamoxifen therapy were found to have different effects.2 Therefore, both absolute rates of local and regional recurrence and the proportional reductions with the more extensive treatment should be listed for each trial. The studies should first be grouped according to local and regional effectiveness and should only then be subdivided according to clinical and pathological evidence of nodal status.
Improved local and regional control is unlikely to change the overall prognosis much, if at all, in patients likely to have subclinical metastatic disease at presentation.3 Trials that used systemic therapy routinely and those that did not should therefore be separated, then subgrouped according to clinical and pathological evidence of nodal status.
Some treatments in the studies analyzed are obsolete (e.g., orthovoltage radiotherapy, radical mastectomy, and single-agent chemotherapy). It would be helpful to group together the trials that used only therapies currently in widespread use. For example, some trials accepted (exclusively or predominantly) patients with histologic evidence of positive nodes who were treated only with modified radical mastectomy and multiagent chemotherapy and were randomly assigned either to receive megavoltage radiotherapy or not to receive it (the Danish BCG 82b, BCCA Vancouver, Helsinki, and BMFT 03 Germany trials). With the use of the values for O – E (the difference between the observed and the expected number of events) and variance in Figure 1, the mean (±SD) odds reduction for mortality among the irradiated patients was 20.8±9 percent (P = 0.02). (Some of the trials in Figure 1 were not described in detail in the Collaborative Group's prior report4 or elsewhere, so I cannot be certain I have included all the relevant studies.)
Finally, the human condition is such that the odds ratio for mortality in any trial will eventually become unity. Therefore, I suggest that the number of deaths from breast cancer, the risk of any recurrence, and the median follow-up among surviving patients at the time of the last data entry be provided separately for each trial, as well as in the aggregate.
4 ReferencesAbram Recht, M.D.
Harvard Medical School, Boston, MA 021151
Early Breast Cancer Trialists' Collaborative Group
Full Text | Web of Science | Medline2
Early Breast Cancer Trialists' Collaborative Group
Web of Science | Medline3
Hellman S . Natural history of small breast cancers. J Clin Oncol 1994;12:2229-2234
Web of Science | Medline4
Early Breast Cancer Trialists' Collaborative Group. Treatment of early breast cancer. Vol. 1. Worldwide evidence, 1985-1990. Oxford, England: Oxford University Press, 1990.
Author/Editor Response
The authors reply:
To the Editor: In our overview of randomized trials of radiotherapy in patients with early breast cancer, we found no clearly significant differences in survival, either when each trial was considered separately or when a meta-analysis of all the results was performed. Overall, 40 percent of the patients assigned to radiotherapy and 41 percent of those assigned to the control group died — a nonsignificant difference. It is therefore entirely possible that unduly selective emphasis and the play of chance are chiefly responsible for the marginally significant survival advantage that Dr. Recht finds when he restricts his attention to just 4 of the studies (and ignores the other 32).
Richard Peto, M.A., M.Sc.
Richard Gray, M.A., M.Sc.
Rory Collins, M.B., B.S., M.Sc.
Radcliffe Infirmary, United Kingdom- Citing Articles (2)
