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Treatment of oestrogen deficiency in women with previous breast cancer

breast cancer is becoming an important aspect of their care. This is mainly attributable to the more widespread use of tamoxifen, chemotherapy and gonadotrophin-releasing hormone agonists in the treatment of this disease, which antagonise or suppress the effects of endogenous oestrogens and may induce a premature menopause. Up to two-thirds of patients can experience oestrogen deficiency symptoms and these have been shown to have a significant, negative effect on quality of life.1 Whilst osteoporosis and arterial disease prevention are important objectives for women surviving breast cancer, the treatment of oestrogen deficiency symptoms presents the most significant clinical dilemma given the uncertainty the aetiology of this disease but lack of equally efficacious alternatives for symptom relief. Alternatives to hormone replacement therapy (HRT) that are often prescribed to breast cancer patients are either no more effective than placebo (eg, evening primrose oil, clonidine, vitamin E, soy phytoestrogens), or have not been evaluated in placebo-controlled trials (eg, serotonin uptake inhibitors, complementary therapies).2 Low-dose progestogens and tibolone appear to confer significant symptom control but long-term controlled data on their efficacy and safety in breast cancer survivors are lacking.3,4 The most recent and comprehensive re-analysis of observational HRT studies reported an increase in breast cancer risk with long-term exposure (calculated relative risk for a median duration of use of 11 years 1.35, 95% confidence interval 1.21-1.49). In absolute terms, this probably accounts for only two extra cancers per 1,000 women who use HRT for five years.5 These estimates are primarily based on unopposed oestrogen exposure. Combined HRT also appears to increase risk when taken long-term but it is not possible to determine from current data whether this is equivalent to, or greater than that conferred by oestrogen alone and if risk is influenced by the progestin class (ie, C21 progesterone or 19-nor testosterone derivatives), or prescription pattern (ie, continuous or cyclic). Irrespective of the type of HRT prescribed, breast cancer risk decreases following its cessation suggesting a growthpromoting effect only. However, this growth promotion does not appear to adversely affect breast cancer prognosis if it is taken prior to a breast cancer diagnosis and a growing number of observational studies of HRT in breast cancer patients have failed to demonstrate any reduction in diseasefree survival or mortality, regardless of whether unopposed, continuous combined or sequential HRT was allocated.6 Given that short-term use of HRT does not seem to increase risk and in view of its proven efficacy in treating oestrogendeficiency symptoms, HRT is being prescribed increasingly to breast cancer patients on an ad hoc basis.7,8 This will not add to current knowledge and it is recommended that controlled trials are conducted.9 Based on the successful implementation of a pilot randomised study in the UK, large-scale trials have now been initiated in Scandinavia and a national UK trial is planned. It is essential, however, that HRT alternatives also be evaluated as rigorously to enable patients and their clinicians reach fully informed decisions.