Knowing the status of the progesterone receptor (PR) in women with estrogen receptor (ER)-positive breast tumors may have important clinical relevance, including how these tumors respond to tamoxifen, according to a new study.

Many breast cancer therapies have been developed for women whose tumors overexpress ER (i.e., ER-positive tumors). However, data suggest that tumors that are ER-positive but PR-negative are less sensitive to tamoxifen compared with those that are ER- and PR-positive.

To determine whether breast tumors that are ER-positive and PR-negative are more likely to be aggressive than ER-positive/PR-positive tumors, Richard M. Elledge, M.D., of the Baylor College of Medicine in Houston, and colleagues conducted a retrospective clinical analysis of more than 44,000 breast cancer patients with ER-positive tumors. They compared clinical and biologic features of the tumors based on PR status. In addition, the researchers examined HER-1 and HER-2 status in a subset of more than 1,700 patients.

The authors found that the ER-positive/PR-negative tumors--which were larger, divided more rapidly and were more likely to have an abnormal number of chromosomes than the ER- and PR-positive tumors--also more often expressed HER-1 and overexpressed HER-2. Recurrence was higher among tamoxifen-treated women with ER-positive/PR-negative tumors that expressed HER-1 or HER-2 but not among women with ER- and PR-positive tumors that expressed these growth factor receptors. The authors conclude that the lack of PR expression in ER-positive tumors may be a marker of aberrant growth factor signaling that could contribute to tamoxifen resistance.

In an editorial, Cindy A. Wilson, Ph.D., and Dennis J. Slamon, M.D., Ph.D., of the David Geffen School of Medicine at the University of California Los Angeles, discuss how these findings support new hypotheses regar
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Contact: Sarah L. Zielinski
jncimedia@oxfordjournals.org
301-841-1287
Journal of the National Cancer Institute
6-Sep-2005