WITHDRAWN: Multi-agent chemotherapy for early breast cancer.

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Cochrane Database Syst Rev. 2008 Oct 8;(4):CD000487.Cochrane Database Syst Rev. 2002;(1):CD000487.
WITHDRAWN: Multi-agent chemotherapy for early breast cancer.Clarke MJ.UK Cochrane Centre, National Institute for Health Research, Summertown Pavilion, Middle Way, Oxford, UK, OX2 7LG.BACKGROUND:
There have been many randomised trials of adjuvant prolonged
polychemotherapy among women with early breast cancer, and an updated
overview of their results is presented. OBJECTIVES: In this report, the
Early Breast Cancer Trialists' Collaborative Group present their
updated systematic overview (meta-analysis) of treatment with
polychemotherapy. SEARCH STRATEGY: Trial identification procedures for
the EBCTCG overviews have been described elsewhere. See under "EBCTCG"
in the Breast Cancer Collaborative Review Group module.
SELECTION
CRITERIA:
All randomised trials that began before 1990 and involved
treatment groups that differed only with respect to the chemotherapy
regimens that were being compared.
DATA COLLECTION AND ANALYSIS: In
1995, information was sought on each woman in any randomised trial that
began before 1990 and involved treatment groups that differed only with
respect to the chemotherapy regimens that were being compared. Analyses
involved about 18,000 women in 47 trials of prolonged polychemotherapy
versus no chemotherapy, about 6000 in 11 trials of longer versus
shorter polychemotherapy, and about 6000 in 11 trials of
anthracycline-containing regimens versus CMF (cyclophosphamide,
methotrexate, and fluorouracil).
MAIN RESULTS: For recurrence,
polychemotherapy produced substantial and highly significant
proportional reductions both among women aged under 50 at randomisation
(35% [SD 4] reduction; 2p<0.00001) and among those aged 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 recurrence
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
proportional reductions in risk were similar for women with
node-negative and node-positive disease. Applying the proportional
mortality reduction 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-positive disease to 53% (an absolute
benefit of 11%). The smaller proportional mortality reduction observed
in all women aged 50-69 at randomisation would translate into smaller
absolute benefits, changing a 10-year survival of 67% for those with
node-negative disease to 69% (an absolute gain of 2%) and of 46% for
those with node-positive disease to 49% (an absolute gain of 3%).
The
age-specific benefits of polychemotherapy appeared to be largely
irrespective of menopausal status at presentation, oestrogen receptor
status of the primary tumour, and of whether adjuvant tamoxifen had
been given. In terms of other outcomes, there was a reduction of about
one-fifth (2p=0.05) in contralateral breast cancer, which has already
been included in the analyses of recurrence, and no apparent adverse
effect on deaths from causes other than breast 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 comparisons did
suggest that, compared with CMF alone, the anthracycline-containing
regimens studied produced somewhat greater effects on recurrence
(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. AUTHORS'

CONCLUSIONS: Some months of adjuvant polychemotherapy (eg, with CMF or
an anthracycline-containing regimen) typically produces an absolute
improvement of about 7-11% in 10-year survival for women aged under 50
at presentation with early 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 treatment, and this report makes no
recommendations as to who should or should not be treated.