Estrogen receptor alpha gene ESR1 amplification may predict endocrine therapy responsiveness in breast cancer patients

Estrogen receptor (ER) alpha plays a crucial role in normal breast development and has also been linked to mammary carcinogenesis and clinical outcome in breast cancer patients. However, the molecular mechanisms controlling the expression of ER alpha are as yet not fully understood. Gene amplification is one of the important factors regulating protein expression. Recent studies on the amplification of the ESR1 gene, which encodes ER alpha, have presented conflicting data. Using fluorescence in situ hybridization and real-time quantitative polymerase chain reaction analysis, we examined the ESR1 status in a series of breast cancer tissues and analyzed its clinical importance. ESR1 gene amplification and gain were found in 22.6 and 11.3% of samples, respectively, as determined by three-dimensional fluorescence in situ hybridization assay. Moreover, ESR1 amplification and amplification plus gain were significantly negatively correlated with tumor size, number of positive lymph nodes, negative ER alpha, and positive human epidermal growth factor receptor 2 status. It has also been shown that ESR1 amplification strongly correlates with higher expression levels of ER protein and that patients with ESR1 amplification in their tumors apparently experience longer disease-free survival than those without. Our data suggest that ESR1 amplification might prove to be helpful in selecting patients who may potentially benefit from endocrine therapy. (Cancer Sci 2009; 100: 1012-1017).