Genes Regulated by Estrogen Predict Survival in Hormone-Positive Breast Cancers

Charles Perou, Ph.D.
University of North Carolina Chapel Hill
U19ES11391

Background: Breast cancers are classified as hormone receptor positive or negative depending upon whether cell surfaces contain significant levels of estrogen or progesterone receptors. This is a necessary step in determining whether women with breast cancer should be given anti-estrogen therapies such as tamoxifen or aromatase inhibitors. Aromatase inhibitors are considered the standard of care for post-menopausal women with hormone receptor-positive breast cancer; tamoxifen remains the hormonal treatment of choice for pre-menopausal women.

The prognosis of patients with hormone receptor-positive breast cancer can be highly variable, but the causes of this variably are largely unknown. Recent research has shown that estrogen receptor-positive tumors may be divided into at least three subtypes with different patient outcomes.

Advance: To address this concern, researchers at the Lineberger Comprehensive Cancer Center at the University of North Carolina hypothesized that differential expression of estrogen-regulated genes is useful in predicting patient outcome in breast cancer. They first identified estrogen-regulated genes by treating an estrogen receptor-positive breast cancer cell line with estradiol and performing microarray analysis. The researchers then applied this gene-set to 65 primary breast cancer tumors. Further analyses refined the gene-set to 822 genes that optimally defined two groups based on the genes activated in the tumors. The poor-prognosis group showed high expression of cell proliferation and antiapoptosis genes, while the good-prognosis group showed high expression of estrogen and GATA3-regulated genes.

Implications: This study shows that this set of estrogen-regulated genes may be useful in predicting the survival outcome and recurrence of cancer in hormone-receptor positive breast cancer patients treated with tamoxifen. The researchers suggest additional studies are necessary focusing on whether the two groups gain similar benefits from chemotherapy and whether the poor-prognosis group might do better alternative therapies to tamoxifen.

Citation: Oh DS, Troester MA, Usary J, Hu Z, He X, Fan C, Wu J, Carey LA, Perou CM. Estrogen-regulated genes predict survival in hormone receptor-positive breast cancers. J Clin Oncol. 2006 Apr 10;24(11):1656-64.