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"Effects of chemotherapy and
hormonal therapy for early
breast cancer on
recurrence and 15-year survival: an overview of the randomised trials,"
by the Early Breast Cancer Trialists' Collaborative Group (O. Abe, et al.),
The Lancet, 365(9472): 1687-1717, 14 May 2005.
[Authors affiliations: c. 140 institutions
worldwide]
Abstract: "Background
Quinquennial overviews (1985-2000) of the randomised trials in early breast
cancer have
assessed the 5-year and 10-year effects of various systemic adjuvant
therapies on breast cancer recurrence and survival. Here, we report the
10-year and 15-year effects. Methods Collaborative meta-analyses were
undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or
hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide,
methotrexate, fluorouracil), anthracycline-based combinations such as FAC
(fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil,
epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none
involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors.
Findings Allocation to about 6 months of anthracycline-based
polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer
death rate by about 38% (SE 5) for women younger than 50 years of age when
diagnosed and by about 20% (SE 4) for those of age 50-69 years when
diagnosed, largely irrespective of the use of tamoxifen and of oestrogen
receptor (ER) status, nodal status, or other tumour characteristics. Such
regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for
breast cancer mortality) more effective than CMF chemotherapy. Few women of
age 70 years or older entered these chemotherapy trials.
"For ER-positive disease only, allocation to about 5 years of adjuvant
tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely
irrespective of the use of chemotherapy and of age (<50, 50-69, >= 70
years), progesterone receptor status, or other tumour characteristics. 5
years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast
cancer mortality) more effective than just 1-2 years of tamoxifen. For
ER-positive tumours, the annual breast cancer mortality rates are similar
during years 0-4 and 5-14, as are the proportional reductions in them by 5
years of tamoxifen, so the cumulative reduction in mortality is more than
twice as big at 15 years as at 5 years after diagnosis.
"These results combine six meta-analyses: anthracycline-based versus no
chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000);
anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of
tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33
000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally,
allocation to ovarian ablation or suppression (8000 women) also
significantly reduces breast cancer mortality, but appears to do so only in
the absence of other systemic treatments.
"For middle-aged women with ER-positive disease (the commonest type of
breast cancer), the breast cancer mortality rate throughout the next 15
years would be approximately halved by 6 months of anthracycline-based
chemotherapy (with a combination such as FAC or FEC) followed by 5 years of
adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and
20% (age 50-69 years) from such chemotherapy were followed by a further
reduction of 31% from tamoxifen in the risks that remain, the final
mortality reductions would be 57% and 45%, respectively (and, the trial
results could well have been somewhat stronger if there had been full
compliance with the allocated treatments). Overall survival would be
comparably improved, since these treatments have relatively small effects on
mortality from the aggregate of all other causes.
"Interpretation Some of the widely practicable adjuvant drug treatments
that were being tested in the 1980s, which
substantially reduced 5-year recurrence rates (but had somewhat less effect
on 5-year mortality rates), also substantially reduce 15-year mortality
rates. Further improvements in long-term survival could well be available
from newer drugs, or better use of older drugs."
This 2005 report from The Lancet was
cited 49 times in current journal articles indexed by Thomson
Scientific during November-December 2006. Only one other medicine paper
published in the last two years (aside from reviews) garnered a greater
number of citations during that two-month period. Prior to the most recent
bimonthly count, citations to the paper have accrued as follows:
September-October 2006: 34 citations
July-August 2006: 39
May-June 2006: 34
March-April 2006: 26
January-February 2006: 31
November-December 2005: 28
September-October 2005: 11
July-August 2005: 9
May-June 2005: 2
Total citations to date: 263
SOURCE: Hot
Papers Database (Included with a subscription to the print newsletter Science
Watch®, available from the
Research Services Group. Packaged on a CD that is mailed with each Science
Watch issue, the Hot
Papers Database contains data on hundreds of highly cited papers published
during the last two years. User interface permits searching by author,
organization, journal, field, and more. Total citations, as well as citations
accrued during successive bimonthly periods, can be assessed and graphed. An
updated CD containing the most recent bimonthly data is mailed with every new
issue of Science
Watch,
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