Hormonal treatment of advanced breast cancer

Endocrine therapy for breast cancer has been used for almost a century, but because of the enormous success of tamoxifen there has been a resurgence of interest by the pharmaceutical industry to develop new and innovative endocrine therapies. Overall, the strategy is quite simple. Estrogen stimulates growth; therefore, the goal is to deny the breast tumor estrogens. Tamoxifen accomplishes this by blocking the estrogen receptor. The new antiestrogens, toremifene and droloxifene, however, appear to have no greater activity than tamoxifen in the treatment of advanced disease and therefore may ultimately offer no advantages over current therapy. In contrast, the pure antiestrogens hold additional promise as they may produce a more profound inhibitory effect on the tumor, and the response may be maintained longer. An orally active, pure antiestrogen, however, would be an important advance. The strategy of using GnRH agonists for premenopausal patients clearly has merit to produce a chemical oophorectomy. The strategy could be integrated into the general treatment plan for the young premenopausal patient taking tamoxifen who may not have had her menstrual cycles stopped by combination chemotherapy. The GnRH agonists would block the reflex rise in estradiol caused by tamoxifen therapy and ultimately produce a more efficient antihormonal therapy. Indeed, the different specific aromatase inhibitors can also be integrated into the treatment plan to produce a complete estrogen blockade. Whether the use will be found to be superior to pure antiestrogens, however, must await the completion of comparative clinical studies. If all the results of endocrine therapy are therapeutically similar, the final strategy may depend on the acceptability by the patient of an individual delivery method for each pharmaceutical approach.