Endocrine Abstracts

The importance of endogenous hormones in the aetiology of breast cancer has long been evident from the strong relationships between breast cancer risk and certain aspects of a woman’s reproductive history1. More recently, the risk of developing breast cancer among postmenopausal women has also been shown to increase substantially with increasing levels of circulating oestradiol2, thus providing more direct evidence for the role of hormones in the development of the disease. The relationship between endogenous hormones and breast cancer risk leads naturally to the question of whether exogenous hormones, such as oral contraceptives and postmenopausal hormone therapy, also affect breast cancer risk and this review focuses on the risks associated with such hormonal therapies.In terms of combined oral contraceptive use, recency of use is the key determinant of breast cancer risk. While women are taking combined oral contraceptives there is a small but definite increase in the risk of having breast cancer diagnosed relative to never users, but once use ceases this increase declines and by about 10 years after ceasing use past users are no longer at increased risk3. However, since the background risk of breast cancer is relatively low during a woman’s 20s and 30s, use of oral contraceptives during this period does not result in any substantial increase in the lifetime risk of breast cancer. There is considerably less information about the effects of progestagen-only oral contraceptives and depot-progestagens but the limited available data suggest that their effects might be similar to those of combined preparations.Observational studies and randomised trials have consistently shown that use of HRT increases the risk of breast cancer4-7. Overall, the evidence suggests that the risk of breast cancer is increased while women are taking HRT but that this effect wears off soon after stopping, with breast cancer risk returning to that among non-users within a few years after ceasing use. Among current users the risk of breast cancer increases with increasing duration of use. Furthermore, although there is evidence of an increase in risk among current and recent users of all types of HRT, there is a substantially greater increase in risk associated with use of combined HRT compared to oestrogen only HRT. Body mass index has been shown consistently to modify the relationship between HRT and breast cancer risk such that the increase in risk associated with use is materially greater among leaner women compared to fatter women. On the basis of the available evidence, it is estimated that HRT use for 5 years leads to an extra 1.5 cases per thousand users of oestrogen only therapy, and an extra 6 cases per thousand users of combined therapy.To date, there is relatively little reliable information on the effect of exogenous hormone use on mortality from breast cancer. However, trial data have shown that breast cancers diagnosed in women allocated to HRT had a significantly larger size than cancers in non-users of HRT7 and preliminary results from the Million Women Study are suggestive of a slight increase in mortality among current users of HRT4. Longer follow-up of this and other cohorts and further information on the effects of different patterns of HRT use on mortality from breast cancer are needed.