POLYCHEMOTHERAPY FOR EARLY BREAST-CANCER - AN OVERVIEW OF THE RANDOMIZED TRIALS

Background There have been many randomised trials of adjuvant prolonge d polychemotherapy among women with early breast cancer, and an update d overview of their results is presented. Methods In 1995, information was sought on each woman in any randomised trial that began before 19 90 and involved treatment groups that differed only with respect to th e chemotherapy regimens that were being compared. Analyses involved ab out 18 000 women in 47 trials of prolonged polychemotherapy versus no chemotherapy, about 6000 in 11 trials of longer versus shorter polyche motherapy, and about 6000 in 11 trials of anthracycline-containing reg imens versus CMF (cyclophosphamide, methotrexate, and fluorouracil). F indings For recurrence, polychemotherapy produced substantial and high ly significant proportional reductions both among women aged under 50 at randomisation (35% [SD 4] reduction; 2p<0.00001) and among those ag ed 50-69 (20% [SD 3] reduction; 2p<0.00001); few women aged 70 or over had been studied. For mortality, the reductions were also significant both among women aged under 50 (27% [SD 5] reduction; 2p<0.00001) and among those aged 50-69 (11% [SD 3] reduction; 2p=0.0001). The recurre nce reductions emerged chiefly during the first 5 years of follow-up, whereas the difference in survival grew throughout the first 10 years. After standardisation for age and time since randomisation, the propo rtional reductions in risk were similar for women with node-negative a nd node-positive disease. Applying the proportional mortality reductio n observed in all women aged under 50 at randomisation would typically change a 10-year survival of 71% for those with node-negative disease to 78% (an absolute benefit of 7%), and of 42% for those with node-po sitive disease to 53% (an absolute benefit of 11%). The smaller propor tional mortality reduction observed in all women aged 50-69 at randomi sation would translate into smaller absolute benefits, changing a 10-y ear survival of 67% for those with node-negative disease to 69% (an ab solute gain of 2%) and of 46% for those with node-positive disease to 49% (an absolute gain of 3%). The age-specific benefits of polychemoth erapy appeared to be largely irrespective of menopausal status at pres entation, oestrogen receptor status of the primary tumour, and of whet her adjuvant tamoxifen had been given. In terms of other outcomes, the re was a reduction of about one-fifth (2p=0.05) in contralateral breas t cancer, which has already been included in the analyses of recurrenc e, and no apparent adverse effect on deaths from causes other than bre ast cancer (death rate ratio 0.89 [SD 0.09]). The directly randomised comparisons of longer versus shorter durations of polychemotherapy did not indicate any survival advantage with the use of more than about 3 -6 months of polychemotherapy. By contrast, directly randomised compar isons did suggest that, compared with CMF alone, the anthracycline-con taining regimens studied produced somewhat greater effects on recurren ce (2p=0.006) and mortality (69% vs 72% 5-year survival; log-rank 2p=0 .02). But this comparison is one of many that could have been selected for emphasis, the 99% CI reaches zero, and the results of several of the relevant trials are not yet available. Interpretation Some months of adjuvant polychemotherapy (eg, with CMF or an anthracycline-contain ing regimen) typically produces an absolute improvement of about 7-11% in 10-year survival for women aged under 50 at presentation with earl y breast cancer, and of about 2-3% for those aged 50-69 (unless their prognosis is likely to be extremely good even without such treatment). Treatment decisions involve consideration not only of improvements in cancer recurrence and survival but also of adverse side-effects of tr eatment, and this report makes no recommendations as to who should or should not be treated.