Tamoxifen is a selective estrogen receptor modulator (SERM) used to treat estrogen receptor-positive breast cancers and prevent recurrence of the disease. However, tamoxifen often loses effectiveness over time and can subsequently stimulate breast cancer growth. New endocrine therapies, such as aromatase inhibitors and the antiestrogen fulvestrant, are being are used to augment the effects of tamoxifen, although some studies are suggesting that low levels of estrogen may also inhibit the growth of tamoxifen-stimulated breast tumors.

Clodia Osipo, Ph.D., and V. Craig Jordan, Ph.D., D.Sc., of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University in Chicago, and their colleagues examined the effect of tamoxifen, the estrogen estradiol, and fulvestrant, both alone and in various combinations, in a mouse model of tamoxifen-stimulated human breast cancer.

The researchers found that low levels of estradiol caused tamoxifen-resistant breast tumors to regress, apparently by increasing apoptosis (cell suicide) through decreased expression of Her2/neu and NF-κB, two factors that inhibit apoptosis, and increased expression of the death receptor protein Fas, which regulates apoptosis.

Combined treatment with fulvestrant plus estradiol unexpectedly promoted the growth of tamoxifen-stimulated breast tumors, suggesting that the use of fulvestrant in patients with sufficient levels of circulating estrogen may actually stimulate tumor growth.

In the second study, Hong Liu, M.D., Ph.D., of the Robert H. Lurie Comprehensive Cancer Center, Jordan, and their colleagues examined whether low doses of estradiol would also have an
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Contact: Linda Wang
jncimedia@oupjournals.org
301-841-1287
Journal of the National Cancer Institute
31-Dec-2000