EFFECTS OF RADIOTHERAPY AND SURGERY IN EARLY BREAST-CANCER - AN OVERVIEW OF THE RANDOMIZED TRIALS

Background. Randomized trials of radiotherapy and surgery for early br east cancer may have been too small to detect differences in long-term survival and recurrence reliably. We therefore performed a systematic overview (meta-analysis) of the results of such trials. Methods. Info rmation was sought on each subject from investigators who conducted tr ials that began before 1985 and that compared local therapies for earl y breast cancer. Data on mortality were available from 36 trials compa ring radiotherapy plus surgery with the same type of surgery alone, 10 comparing more-extensive surgery with less-extensive surgery, and 18 comparing more-extensive surgery with less-extensive surgery plus radi otherapy. Information on mortality was available for 28,405 women (97. 4 percent of the 29,175 women in the trials). Results. The addition of radiotherapy to surgery resulted in a rate of local recurrence that w as three times lower than the rate with surgery alone, but there was n o significant difference in 10-year survival; among a total of 17,273 women enrolled in such trials, mortality was 40.3 percent with radioth erapy and 41.4 percent without radiotherapy (P=0.3). Radiotherapy was associated with a reduced risk of death due to breast cancer (odds rat io, 0.94; 95 percent confidence interval, 0.88 to 1.00; P=0.03), which indicates that, after 10 years, there would be about 0 to 5 fewer dea ths due to breast cancer per 100 women. However, there was an increase d risk of death from other causes (odds ratio, 1.24; 95 percent confid ence interval, 1.09 to 1.42; P=0.002). This, together with the age-spe cific death rates, implies, after 10 years, a few extra deaths not due to breast cancer per 100 older women or per 1000 younger women, Durin g the first decade or two after diagnosis, the excess in the rate of s uch deaths that was associated with radiotherapy was much greater amon g women who were over 60 years of age at randomization (15.3 percent v s. 11.1 percent [339 vs. 249 deaths]) than among those under 50 (2.5 p ercent vs. 2.0 percent [62 vs. 49 deaths]). Breast-conserving surgery involved some risk of recurrence in the remaining tissue, but no signi ficant differences in overall survival at 10 years were found in the s tudies of mastectomy versus breast-conserving surgery plus radiotherap y (4891 women), more-extensive surgery versus less-extensive surgery ( 4818 women), or axillary clearance versus radiotherapy as adjuncts to mastectomy (4370 women). Conclusions. Some of the local therapies for breast cancer had substantially different effects on the rates of loca l recurrence - such as the reduced recurrence with the addition of rad iotherapy to surgery - but there were no definite differences in overa ll survival at 10 years.