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ABSTRACT: Estimates of the likely prophylactic effect of tamoxifen
in women with high risk BRCA1 and BRCA2 mutations
The development of breast cancer control strategies in women at
high genetic risk of breast cancer is an important issue. The
likely benefit of chemopreventive approaches is of particular
interest.
Tamoxifen tends to be more effective in both prevention
and treatment of oestrogen receptor positive tumours than oestrogen
receptor negative.
In this study, we combine the oestrogen-receptor
specific effects of tamoxifen from randomized preventive or therapeutic
trials with the oestrogen receptor status of tumours in BRCA1
and BRCA2 mutation positive women from published tumour surveys
to obtain estimates of the likely effect of tamoxifen administration
in mutation carriers.
We used a simple two-stage procedure to
estimate the benefit as a weighted average of the effect on oestrogen
receptor positive tumours and oestrogen receptor negative, and
using a more complex hierarchical modelling approach. Using the
simple procedure and deriving the estimates of benefit from both
primary prevention and therapeutic trials, we obtain an estimated
reduction in risk of breast cancer from administration of tamoxifen
in BRCA1 mutation positive women of 13% (RR=0.87, 95% CI 0.68-1.11).
The corresponding estimated reduction in BRCA2 mutation positive
women was 27% (RR=0.73, 95% CI 0.59-0.90).
Using the more
complex models gave essentially the same results. Using only
the primary prevention trials gave smaller estimates of benefit
in BRCA1 carriers but larger estimates in BRCA2, in both cases
with wider confidence intervals.
The benefit of prophylactic
use of tamoxifen in BRCA1 mutation carriers is likely to be modest,
and the effect in BRCA2 mutation carriers somewhat greater.
[02/04/2002; British Journal of Cancer]
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