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 (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 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,"
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.