Questions raised over use of long-term of tamoxifen
therapy for prevention
Researchers have raised questions over the general
use of tamoxifen as preventive therapy in healthy women at risk of breast
cancer, although benefits were found for women at particularly high risk.
Dr Phyllis Will, Health Analysis and Modelling Group,
Statistics Canada, Ottawa, and colleagues conducted an analysis to estimate
the net health benefits of tamoxifen use in women at high risk of breast
cancer. The analysis follows debate over the potential adverse effects
of preventive tamoxifen therapy, particularly its impact on cardiovascular
disease.
The analysis used breast cancer risk criteria based
on the Breast Cancer Prevention Trial (BCPT) published in 1998, which
found that tamoxifen reduced risk of breast cancer by 49 per cent in high-risk
women.
Applying the criteria to all Canadian women, Dr
Will and colleagues found that 85 per cent would be eligible at some point
in their life for tamoxifen preventive therapy. Although the burden of
breast cancer would fall, tamoxifen therapy would result in increases
in the burdens of coronary heart disease, endometrial cancer, stroke,
hip fracture and cataracts. A decrease in life expectancy of 0.04 years
(approximately two weeks) would be expected.
The researchers then analysed whether or not tamoxifen
therapy would be beneficial in subsets of women at even higher risk of
breast cancer than the BCPT trial identified. Women who had a predicted
five-year breast cancer risk of 3.32 per cent or above could expect a
significant increase in life expectancy as a result of tamoxifen therapy.
The researchers comment: "Although tamoxifen has
a substantial benefit in reducing breast cancer incidence and mortality,
the detrimental effects of tamoxifen on endometrial cancer, coronary heart
disease, stroke and deep vein thrombosis may counter-balance the protective
effect tamoxifen has on breast cancer for the majority of women meeting
the criteria of the BCPT trial."
The analysis is published in the British Journal
of Cancer (2001;85:1280).
However, Jack Cuzick, the Imperial Cancer Research
Fund's head of mathematics, statistics and epidemiology, commenting on
the study said: "This paper paints an overly negative view of the risks
and does not adequately allow for the severity of breast cancer compared
with the more easily treated side effects."
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First-line anastrozole
Researchers have suggested that anastrozole (Arimidex) should be
considered as standard first-line therapy for breast cancer over
tamoxifen in post-menopausal women with hormone receptor-positive
advanced breast cancer.
The suggestion comes from the results
of a combined analysis of two studies of tamoxifen 20mg daily and
anastrozole 1mg daily in 1,021 women. After 18 months, anastrozole
was superior to tamoxifen in terms of time to progression in women
with receptor-positive tumours (median values 10.7 and 6.4 months,
respectively) and at least equivalent in women with receptor-positive
and unknown receptor tumours. Both treatments were well tolerated
(Cancer 2001;92:2247).
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