Cochrane Database Syst Rev. 2008 Oct 8;(4):CD000485.
WITHDRAWN: Ovarian ablation for early breast cancer.
Clarke MJ.UK Cochrane Centre, National Institute for Health Research, Summertown Pavilion, Middle Way, Oxford, UK, OX2 7LG.BACKGROUND:
Among women with early breast cancer, the effects of ovarian ablation
on recurrence and death have been assessed by several randomised trials
that now have long follow-up.
OBJECTIVES: In this report, the Early
Breast Cancer Trialists' Collaborative Group present their third
5-yearly systematic overview (meta-analysis), now with 15 years'
SEARCH STRATEGY: Trial identification procedures for the
EBCTCG overviews have been described elsewhere. See under "EBCTCG" in
the Breast Cancer Collaborative Review Group module.
CRITERIA: All properly randomised trials that began recruiting before
1990 which compared the ablation or suppression of ovarian function,
sometimes with the addition of prednisone, versus no such adjuvant
treatment for women with operable breast cancer. In practice, all the
trials that can be reviewed here began before 1980, and all involved
surgical or therapeutic ablation.
DATA COLLECTION AND ANALYSIS: In
1995, information was sought on each patient in any randomised trial of
ovarian ablation or suppression versus control that began before 1990.
Data were obtained for 12 of the 13 studies that assessed ovarian
ablation by irradiation or surgery, all of which began before 1980, but
not for the four studies that assessed ovarian suppression by drugs,
all of which began after 1985. Menopausal status was not consistently
defined across trials; therefore, the main analyses are limited to
women aged under 50 (rather than "premenopausal") when randomised.
Oestrogen receptors were measured only in the trials of ablation plus
cytotoxic chemotherapy versus the same chemotherapy alone.
RESULTS: Among 2102 women aged under 50 when randomised, most of whom
would have been premenopausal at diagnosis, 1130 deaths and an
additional 153 recurrences were reported. 15-year survival was highly
significantly improved among those allocated ovarian ablation (52.4 vs
46.1%, 6.3 [SD 2.3] fewer deaths per 100 women, logrank 2p=0.001), as
was recurrence-free survival (45.0 vs 39.0%, 2p=0.0007). The numbers of
events were too small for any subgroup analyses to be reliable. The
benefit was, however, significant both for those with ("node positive")
and for those without ("node negative") axillary spread when diagnosed.
In the trials of ablation plus cytotoxic chemotherapy versus the same
chemotherapy alone, the benefit appeared smaller (even for women with
oestrogen receptors detected on the primary tumour) than in the trials
in the absence of chemotherapy (where the observed survival
improvements were about six per 100 node-negative women and 12 per 100
node-positive women). Among 1354 women aged 50 or over when randomised,
most of whom would have been perimenopausal or postmenopausal, there
was only a non-significant improvement in survival and recurrence-free
AUTHORS' CONCLUSIONS: In women aged under 50 with early
breast cancer, ablation of functioning ovaries significantly improves
long-term survival, at least in the absence of chemotherapy. Further
randomised evidence is needed on the additional effects of ovarian
ablation in the presence of other adjuvant treatments, and to assess
the relevance of hormone-receptor measurements.