ESR1 Expression Predicts Tamoxifen Benefit in Breast CA

Lower expression of ESR1 determines tamoxifen resistance in ER-positive breast tumors

TUESDAY, Sept. 27 (HealthDay News) -- Expression of ESR1 predicts tamoxifen benefit in estrogen receptor (ER)-positive breast cancer, with low levels of expression indicative of tamoxifen resistance, according to a study published online Sept. 26 in the Journal of Clinical Oncology.

Chungyeul Kim, M.D., from the University of Pittsburgh, and colleagues investigated the molecular mechanisms responsible for tamoxifen resistance in ER-positive breast tumors using gene expression profiling and ER protein assays. Gene expression profiling was performed on available paraffin-embedded tumors from two National Surgical Adjuvant Breast and Bowel Project trials that determined the use of tamoxifen as an adjuvant systemic therapy (B-14) and as a preventive agent (P-1).

The investigators found that, of the 16 genes examined, including PGR and ERBB2, ESR1 was the strongest linear predictor of benefit from tamoxifen in tumor samples from trial B-14. Based on the hypothesis that lower levels of ESR1 mRNA in the tamoxifen group may have been the main difference between the treatment and placebo groups in samples from trial P-1, it was observed that expression levels of ESR1 were significantly downregulated by more than two-fold in the ER-positive breast cancer cases in the tamoxifen group. ER-positive breast tumors with low levels of ESR1 expression were not prevented by tamoxifen.

"Low-level expression of ESR1 is a determinant of tamoxifen resistance in ER-positive breast cancer," the authors write.

Several authors disclosed financial relationships with pharmaceutical companies, including Genomic Health.

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