NEW YORK (Reuters Health) - In a mouse model of BRCA1-mutation-related breast cancer, tamoxifen treatment promotes the development of mammary cancer, new research shows. “This is a novel finding and was totally unexpected,” Dr. Patricia A. Furth from Georgetown University in Washington, DC, told Reuters Health.
Dr. Furth reported her team’s study results this week during the 27th annual San Antonio Breast Cancer Symposium, which wraps up Saturday.
“In mice with BRCA1-mutation-related breast cancer, all of the mammary epithelial cells have lost expression of the full-length BRCA1 gene,” Dr. Furth explained, “so it is a nice model for human disease.” These animals develop adenocarcinomas with similar genetic changes to those found in human BRCA1-mutation-related breast cancer.
Dr. Furth and colleagues used this model to evaluate the chemopreventive effect of tamoxifen on the development of mammary preneoplasia and adenocarcinoma.
To their surprise, tamoxifen had no protective effect on mammary cancer development in the BRCA1-depleted mice.
In wild-type mice, tamoxifen treatment induced regression of ductal structures, but in BRCA1-depleted mice, tamoxifen statistically significantly increased ductal growth and the prevalence of mammary hyperplasia.
“We fully expected that tamoxifen would be protective but instead what we found is that it appears that loss of BRCA1 turns tamoxifen into something that acts like an agonist [or] an estrogen to promote the development of the cancer,” Dr. Furth said.
“Significantly,” the team notes in a meeting abstract, “while loss of full-length BRCA1 did not alter the pattern of estrogen receptor expression in normal appearing mammary epithelial cells, estrogen receptor expression was down-regulated in the tamoxifen-induced hyperplasias.”
Clinically, Dr. Furth said, these observations should fuel interest in looking for a similar effect in human tissue culture cells with BRCA1 mutations.
The observations, she added, may also “stimulate more interest perhaps in some of the aromatase inhibitors as an approach for the women with BRCA1 mutations as a preventive, which is something that is not done yet.”
MeSH Headings:Animal Diseases: Congresses: Disease Models, Animal: Health Care Economics and Organizations: Organizations: Genes, BRCA1: Diseases: Health CareCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
