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Adjuvant chemotherapy in oestrogen-receptor-poor breast cancer : patient-level meta-analysis of randomised trials

Clarke, M ; Coates, A S ; Darby, S C ; Davies, C ; Gelber, R D ; Godwin, J ; Goldhirsch, A ; Gray, R ; Peto, R and Pritchard, K I , et al. (2008) In The Lancet 371(9606). p.29-40
Abstract

BACKGROUND: The long-term effects of adjuvant polychemotherapy regimens in oestrogen-receptor-poor (ER-poor) breast cancer, and the extent to which these effects are modified by age or tamoxifen use, can be assessed by an updated meta-analysis of individual patient data from randomised trials.

METHODS: Collaborative meta-analyses of individual patient data for about 6000 women with ER-poor breast cancer in 46 trials of polychemotherapy versus not (non-taxane-based polychemotherapy, typically about six cycles; trial start dates 1975-96, median 1984) and about 14 000 women with ER-poor breast cancer in 50 trials of tamoxifen versus not (some trials in the presence and some in the absence of polychemotherapy; trial start dates... (More)

BACKGROUND: The long-term effects of adjuvant polychemotherapy regimens in oestrogen-receptor-poor (ER-poor) breast cancer, and the extent to which these effects are modified by age or tamoxifen use, can be assessed by an updated meta-analysis of individual patient data from randomised trials.

METHODS: Collaborative meta-analyses of individual patient data for about 6000 women with ER-poor breast cancer in 46 trials of polychemotherapy versus not (non-taxane-based polychemotherapy, typically about six cycles; trial start dates 1975-96, median 1984) and about 14 000 women with ER-poor breast cancer in 50 trials of tamoxifen versus not (some trials in the presence and some in the absence of polychemotherapy; trial start dates 1972-93, median 1982).

FINDINGS: In women with ER-poor breast cancer, polychemotherapy significantly reduced recurrence, breast cancer mortality, and death from any cause, in those younger than 50 years and those aged 50-69 years at entry into trials of polychemotherapy versus not. In those aged younger than 50 years (1907 women, 15% node-positive), the 10-year risks were: recurrence 33% versus 45% (ratio of 10-year risks 0.73, 2p<0.00001), breast cancer mortality 24% versus 32% (ratio 0.73, 2p=0.0002), and death from any cause 25% versus 33% (ratio 0.75, 2p=0.0003). In women aged 50-69 years (3965 women, 58% node-positive), the 10-year risks were: recurrence 42% versus 52% (ratio 0.82, 2p<0.00001), breast cancer mortality 36% versus 42% (ratio 0.86, 2p=0.0004), and death from any cause 39% versus 45% (ratio 0.87, 2p=0.0009). Few were aged 70 years or older. Tamoxifen had little effect on recurrence or death in women who were classified in these trials as having ER-poor disease, and did not significantly modify the effects of polychemotherapy.

INTERPRETATION: In women who had ER-poor breast cancer, and were either younger than 50 years or between 50 and 69 years, these older adjuvant polychemotherapy regimens were safe (ie, had little effect on mortality from causes other than breast cancer) and produced substantial and definite reductions in the 10-year risks of recurrence and death. Current and future chemotherapy regimens could well yield larger proportional reductions in breast cancer mortality.

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published
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keywords
Aged, Antineoplastic Combined Chemotherapy Protocols/pharmacology, Breast Neoplasms/classification, Chemotherapy, Adjuvant, Female, Humans, Middle Aged, Multicenter Studies as Topic, Neoplasm Recurrence, Local, Randomized Controlled Trials as Topic, Receptors, Estrogen/classification
in
The Lancet
volume
371
issue
9606
pages
29 - 40
publisher
Elsevier
external identifiers
  • scopus:37549055451
  • pmid:18177773
ISSN
0140-6736
DOI
10.1016/S0140-6736(08)60069-0
language
English
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yes
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b55ab7b2-7667-4c99-aa75-e2c8af9831a8
date added to LUP
2024-02-06 12:39:10
date last changed
2024-09-10 23:33:03
@article{b55ab7b2-7667-4c99-aa75-e2c8af9831a8,
  abstract     = {{<p>BACKGROUND: The long-term effects of adjuvant polychemotherapy regimens in oestrogen-receptor-poor (ER-poor) breast cancer, and the extent to which these effects are modified by age or tamoxifen use, can be assessed by an updated meta-analysis of individual patient data from randomised trials.</p><p>METHODS: Collaborative meta-analyses of individual patient data for about 6000 women with ER-poor breast cancer in 46 trials of polychemotherapy versus not (non-taxane-based polychemotherapy, typically about six cycles; trial start dates 1975-96, median 1984) and about 14 000 women with ER-poor breast cancer in 50 trials of tamoxifen versus not (some trials in the presence and some in the absence of polychemotherapy; trial start dates 1972-93, median 1982).</p><p>FINDINGS: In women with ER-poor breast cancer, polychemotherapy significantly reduced recurrence, breast cancer mortality, and death from any cause, in those younger than 50 years and those aged 50-69 years at entry into trials of polychemotherapy versus not. In those aged younger than 50 years (1907 women, 15% node-positive), the 10-year risks were: recurrence 33% versus 45% (ratio of 10-year risks 0.73, 2p&lt;0.00001), breast cancer mortality 24% versus 32% (ratio 0.73, 2p=0.0002), and death from any cause 25% versus 33% (ratio 0.75, 2p=0.0003). In women aged 50-69 years (3965 women, 58% node-positive), the 10-year risks were: recurrence 42% versus 52% (ratio 0.82, 2p&lt;0.00001), breast cancer mortality 36% versus 42% (ratio 0.86, 2p=0.0004), and death from any cause 39% versus 45% (ratio 0.87, 2p=0.0009). Few were aged 70 years or older. Tamoxifen had little effect on recurrence or death in women who were classified in these trials as having ER-poor disease, and did not significantly modify the effects of polychemotherapy.</p><p>INTERPRETATION: In women who had ER-poor breast cancer, and were either younger than 50 years or between 50 and 69 years, these older adjuvant polychemotherapy regimens were safe (ie, had little effect on mortality from causes other than breast cancer) and produced substantial and definite reductions in the 10-year risks of recurrence and death. Current and future chemotherapy regimens could well yield larger proportional reductions in breast cancer mortality.</p>}},
  author       = {{Clarke, M and Coates, A S and Darby, S C and Davies, C and Gelber, R D and Godwin, J and Goldhirsch, A and Gray, R and Peto, R and Pritchard, K I and Wood, W C}},
  issn         = {{0140-6736}},
  keywords     = {{Aged; Antineoplastic Combined Chemotherapy Protocols/pharmacology; Breast Neoplasms/classification; Chemotherapy, Adjuvant; Female; Humans; Middle Aged; Multicenter Studies as Topic; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Receptors, Estrogen/classification}},
  language     = {{eng}},
  number       = {{9606}},
  pages        = {{29--40}},
  publisher    = {{Elsevier}},
  series       = {{The Lancet}},
  title        = {{Adjuvant chemotherapy in oestrogen-receptor-poor breast cancer : patient-level meta-analysis of randomised trials}},
  url          = {{http://dx.doi.org/10.1016/S0140-6736(08)60069-0}},
  doi          = {{10.1016/S0140-6736(08)60069-0}},
  volume       = {{371}},
  year         = {{2008}},
}