Endocrine Abstracts

For the last 3 decades tamoxifen has been the mainstay of the endocrine treatment of breast cancer. In early hormone receptor positive disease, 5 years of tamoxifen reduces the annual odds of death by c.25% and this has been a major contributor to the reduction in mortality from breast cancer in the UK since 1988. The generally good tolerability of tamoxifen has also led to its use in trials of chemoprevention where it has been found to reduce the early risk of presenting with breast cancer by c.35%. The mixed agonist/antagonist profile of tamoxifen which differs between tissues and has resulted in tamoxifen and similar drugs being described as selective (o)estrogen receptor modulators (SERMs), created a rationale for the development of 2 other ways of reducing oestrogenic stimulation - oestrogen withdrawal and pure oestrogen antagonism. In postmenopausal women near complete oestrogen withdrawal is achieved with the 3rd generation aromatase inhibitors which have now been shown to be more efficacious and overall better tolerated than tamoxifen. As such they are likely to become the bedrock of endocrine therapy in postmenopausal women over the next few years. The dependence of this greater efficacy on the absence of the agonist activity possessed by tamoxifen is clear from a series of correlative science studies. Studies to assess the role of oestrogen deprivation using GnRH agonists in comparison with tamoxifen in premenopausal women are underway. Trials with the pure antioestrogen fulvestrant are also being conducted to assess the optimal integration of this interesting agent into the armamentorium of endocrine therapy.