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Apr 16, 2007

Amplification of ESR1 Gene Seen in a Fifth of Breast Cancers

  • Researchers have found that 20% women with breast cancer carry extra copies of a particular gene ESR1 (estrogen receptor alpha). They report that such patients are more likely to respond positively to the widely used estrogen blocking drug tamoxifen than are patients who do not carry extra copies of the gene.

    Scientists from the University Medical Center Hamburg-Eppendorf (UKE) and TriStar Technology Group used the company’s high-throughput tissue analysis platform and Affymetrix’ 10K SNP array. The study is published online in Nature Genetics.

    "The findings of this study could lead to genetic tests to determine when and whether tamoxifen should be prescribed as an effective breast cancer treatment," states Ronald Simon, UKE's/TriStar's head of molecular pathology. "The findings also suggest that tamoxifen might, one day, replace or diminish the need for chemotherapy in some women."

    "Because the gene is amplified in women with certain precancerous conditions,” Guido Sauter, TriStar's co-founder and CSO, adds, “tamoxifen might also help prevent breast cancer from developing in women showing its early signs."

    The investigators screened for gene copy number changes in breast cancer tissues collected from patients in Germany and Switzerland and detected amplification of ESR1. They then conducted high-density tissue microarray analysis on more than 2,000 microarrayed clinical breast cancer samples from TriStar's repository.

    The team found amplification in more than a fifth of breast cancers. Of tumors with ESR1 amplification, 99% showed estrogen receptor protein over-expression compared with 66.7% cancers without such amplification.

    In a subsequent study of 175 breast cancer patients who received tamoxifen, survival was significantly higher in those individuals with ESR1-amplified cancers than in those with estrogen-positive cancers without amplification. An additional finding of ESR1 amplification in benign and precancerous breast diseases suggests that ESR1 amplification may be a common mechanism in breast disease and an early genetic alteration in many types of breast cancer.



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