10501 Background: Estrogen receptor alpha (ERα) expression is a prognostic parameter in breast cancer and predicts response to endocrine therapy. One of the factors important for protein expression is amplification of its encoding gene ESR1. We have investigated the value of ESR1 amplification in predicting the long-term clinical outcome in tamoxifen-treated postmenopausal women with endocrine-responsive breast cancer. Methods: 394 patients who had been randomized into the tamoxifen-only arm of the prospectively designed endocrine ABCSG-06 trial and in whom FFPE tumor tissue was available were included in this analysis. Immunohistochemical ERα expression was evaluated both locally and centrally using the Allred score, while ESR1 gene amplification status was evaluated by FISH analysis using the ESR1/CEN6 ratio. Results: ESR1 copy number gains were detected in 187 of 394 (47%) tumor specimen and was associated with favorable clinical outcome. At a median follow-up of 10 years, women with intratumoral ESR1 copy number gains had a significantly longer distant recurrence-free survival (adjusted HR for relapse 0.48; 95% CI 0.28-0.83; p=0.009) and breast cancer-specific survival (adjusted HR for death 0.46; CI 0.46-0.71; p=0.006) when compared to women with normal ESR1 copy numbers. Immunohistochemical ERα protein expression, evaluated by Allred score, was significantly correlated with ESR1 copy number alterations (p<0.0001; Chi-Square test), but did itself not allow to discriminate between patients with poor and good prognosis. Conclusions: ESR1 amplification status is an independent and powerful predictor for long-term distant recurrence-free and breast cancer-specific survival in postmenopausal women with endocrine-responsive early-stage breast cancer who received 5 years of tamoxifen.
OR15-4 Long-Term Follow-Up of a Female with a Mutation in the Estrogen Receptor Alpha (ESR1) Gene
