Therapy for menopausal symptoms during and after treatment for breast cancer - Safety considerations

Breast cancer is the most common newly diagnosed cancer in women. Life-time risk in the US is 1 in 8 (13.2%), in the UK it is 1 in 9 and in Australia it affects 1 in 11 women, of whom approximately 27% will be premenopausal at the time of their diagnosis. Many of these women will experience a sudden menopause as a result of chemotherapy, endocrine therapy or surgical interventions. For these women, the onset of menopausal symptoms is often sudden and severe. The management of such symptoms remains controversial. Women experiencing menopausal symptoms after breast cancer should be encouraged to avoid identifiable triggers for their symptoms and to consider lifestyle modification as a means of controlling those symptoms. When such measures fail, non-hormonal treatments may also be considered. These include clonidine, gabapentin and some antidepressants. Randomised trials have shown a significant difference in the symptom relief associated with various selective serotonin reuptake inhibitors and selective serotonin and noradrenaline (norepinephrine) reuptake inhibitors compared with placebo. Many women elect to use non-prescription complementary therapies to alleviate their menopausal symptoms. Systematic reviews of phytoestrogens have, however, failed to demonstrate significant relief of menopausal symptoms. More than 20 clinical trials have been conducted examining the relationship between postmenopausal hormone replacement therapy and breast cancer recurrence. The majority of these have been observational and have shown no increased risk of recurrence. However, the largest randomised trial that has thus far been conducted was recently halted because of a reported increase in the risk of recurrence amongst users of hormone replacement therapy. Tibolone, a selective tissue estrogen activity regulator, is a compound that exerts clinical effects both by receptor-mediated actions and tissue selective enzyme inhibition, and has been shown in preclinical studies to have different effects to estrogen on the breast. Although tibolone may prove safer than estrogen for long-term use in breast cancer survivors, the results of a large randomised trial are awaited to confirm this. The decision on how best to manage menopausal symptoms must thus be made on an individual basis and after thorough discussion and evaluation of the risks and benefits of each potential intervention.