It is clear from this review that hormonal contraceptives, postmenopausal hormone therapy, and DES are associated with an increase in breast cancer risk. In contrast, results with respect to fertility-enhancing drugs, although broadly reassuring, must still be viewed as equiv ocal. In terms of future research, the most urgent questions concern hormonal contraceptives and postmenopausal hormone therapy since these preparations are currently used by substantial numbers of women throughout the world.
For the most part, the effects of hormonal contraceptives and postmenopausal hormone therapy on breast cancer risk appear to be remarkably consistent across groups of women identified by various characteristics and with different background risks of breast cancer. However, a large number of genes are now known to be involved in hormone metabolism and this raises the question of whether some women are more susceptible than others to the effects of exogenous hormones.28 Existing studies of breast cancer risk in relation to relevant candidate genes are unlikely to have the power to examine such gene-environment interactions and much larger studies will be required in the future to address these issues.
As far as the effects of hormonal contraceptives on breast cancer risk are concerned, there are several areas where more data are needed. Firstly, since use of contraceptives containing only progestagens is rising rapidly, more data are needed to establish whether their effects on breast cancer are really similar to those of combined preparations. Secondly, better data are required on whether women who have used combined oral contraceptives are more likely to have their cancers detected earlier. Finally, data on women whose use ceased more than 20 years ago will be available within the next few years, and this will allow the long-term effects of oral contraceptives on breast cancer risk to be studied in more detail than has previously been possible.
It is now clear that the risk of breast cancer is increased among long-term users of post-menopausal hormone therapy. Although the vast majority of the epidemiological evidence for this association is based on women who had taken preparations containing estrogen alone, more recent studies have consistently found a greater risk of breast cancer in users of combined preparations than in women using estrogen-only preparations. Moreover, results of randomized controlled trials that have predominantly used a single type of combined therapy show a clear in crease in the risk of breast cancer among users compared to a placebo group. Given the trend of increasing use of combination therapy, these observations are clearly disconcerting, particularly for women with an intact uterus, for whom estrogen-only therapy is normally contraindi-cated. There is, therefore, an urgent need for more data on women who have used combined preparations, to provide more accurate and detailed information on the risk of breast cancer associated with such therapy.
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