PARIS, France--New ideas and applications for endocrine therapy in early breast cancer may provide a revolution in our thinking about the nature of the disease, said Dr. M. Baum, of The Royal Marsden Hospital, London. The efficacy of adjuvant tamoxifen(Drug information on tamoxifen) (Nolvadex) therapy in prolonging disease-free survival in postmenopausal women with early breast cancer has been securely established, he said at the Fifth International Congress on Anti-Cancer Chemotherapy.
The next generation of trials, he stressed, must explore the utility of tamoxifen therapy in premenopausal women and in those with negative estrogen-receptor (ER) status, the interaction of tamoxifen with estrogen replacement therapy, the optimum duration of tamoxifen therapy, and the role of tamoxifen in primary therapy.
The conclusion that tamoxifen is effective only in postmenopausal women may well be flawed, Dr. Baum said. The problem, he suggested, may stem from comparisons of chemotherapy plus tamoxifen versus chemotherapy alone, in which the benefits of tamoxifen may be overshadowed or diluted by the effects of chemotherapy.
He challenged the idea that tamoxifen, which causes a paradoxical increase in estradiol(Drug information on estradiol) levels prior to menopause, is a biologically implausible therapy for premenopausal women. "If you believe that there's a simple interaction between estrogen and micrometastases, then you would assume that tamoxifen would make things worse in the premenopausal woman--but that is just not the case," he said.
In fact, he pointed out, the United Kingdom Cancer Research Campaign (CRC) Adjuvant Breast Cancer Trial documented similar 10-year follow-up results in 300 premenopausal women and 660 postmenopausal women who had received tamoxifen.
"The joker in the pack is the unexpected results of the old trials of ovarian ablation," Dr. Baum said. He noted that the Scottish Cancer Trials Group found "superimpossible" 15-year survival curves in premenopausal women who underwent ovarian ablation and in those who received adjuvant chemotherapy.
The question of whether ovarian suppression is equivalent to chemotherapy is particularly important, he stressed, now that currently available luteinizing hormone-releasing hormone (LHRH) analogs offer a reversible alternative to surgical castration or radiation menopause.