Background Randomized trials of radiotherapy and surgery forearly breast cancer may have been too small to detect differencesin long-term survival and recurrence reliably. We thereforeperformed a systematic overview (meta-analysis) of the resultsof such trials.
Methods Information was sought on each subject from investigatorswho conducted trials that began before 1985 and that comparedlocal therapies for early breast cancer. Data on mortality wereavailable from 36 trials comparing radiotherapy plus surgerywith the same type of surgery alone, 10 comparing more-extensivesurgery with less-extensive surgery, and 18 comparing more-extensivesurgery with less-extensive surgery plus radiotherapy. Informationon mortality was available for 28,405 women (97.4 percent ofthe 29,175 women in the trials).
Results The addition of radiotherapy to surgery resulted ina rate of local recurrence that was three times lower than therate with surgery alone, but there was no significant differencein 10-year survival; among a total of 17,273 women enrolledin such trials, mortality was 40.3 percent with radiotherapyand 41.4 percent without radiotherapy (P = 0.3). Radiotherapywas associated with a reduced risk of death due to breast cancer(odds ratio, 0.94; 95 percent confidence interval, 0.88 to 1.00;P = 0.03), which indicates that, after 10 years, there wouldbe about 0 to 5 fewer deaths due to breast cancer per 100 women.However, there was an increased risk of death from other causes(odds ratio, 1.24; 95 percent confidence interval, 1.09 to 1.42;P = 0.002). This, together with the age-specific death rates,implies, after 10 years, a few extra deaths not due to breastcancer per 100 older women or per 1000 younger women. Duringthe first decade or two after diagnosis, the excess in the rateof such deaths that was associated with radiotherapy was muchgreater among women who were over 60 years of age at randomization(15.3 percent vs. 11.1 percent [339 vs. 249 deaths]) than amongthose under 50 (2.5 percent vs. 2.0 percent [62 vs. 49 deaths]).Breast-conserving surgery involved some risk of recurrence inthe remaining tissue, but no significant differences in overallsurvival at 10 years were found in the studies of mastectomyversus breast-conserving surgery plus radiotherapy (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 hadsubstantially different effects on the rates of local recurrence such as the reduced recurrence with the addition ofradiotherapy to surgery but there were no definite differencesin overall survival at 10 years.
Source Information
The Early Breast Cancer Trialists' Collaborative Group Secretariat (Mike Clarke, Rory Collins, Jon Godwin, Richard Gray, and Richard Peto) assumes full responsibility for the overall content and integrity of this manuscript.
Address reprint requests to the EBCTCG Secretariat, ICRF/MRC Clinical Trial Service Unit, Nuffield Department of Clinical Medicine, Radcliffe Infirmary, Oxford OX2 6HE, United Kingdom.
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