Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Singer, CF; Holst, F; Steurer, S; Burandt, EC; Lax, SF; Jakesz, R; Rudas, M; Stoger, H; Greil, R; Sauter, G; Filipits, M; Simon, R; Gnant, M; Abcsg, ABCSG.
Estrogen Receptor Alpha Gene Amplification Is an Independent Predictor of Long-Term Outcome in Postmenopausal Patients with Endocrine-Responsive Early Breast Cancer
CLIN CANCER RES. 2022; 28(18): 4112-4120.
Doi: 10.1158/1078-0432.CCR-21-4328
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- Co-authors Med Uni Graz
- Lax Sigurd
- Stöger Herbert
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- Abstract:
- Purpose: Estrogen receptor (ER) expression is a prognostic parameter in breast cancer, and a prerequisite for the use of endocrine therapy. In ER+ early breast cancer, however, no receptor-associated biomarker exists that identifies patients with a particularly favorable outcome. 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. Experimental Design: 394 patients who had been randomized into the tamoxifen-only arm of the prospective randomized ABCSG-06 trial of adjuvant endocrine therapy with available formalin-fixed, paraffin-embedded tumor tissue were included in this analysis. IHC ERa expression was evaluated both locally and in a central lab using the Allred score, while ESR1 gene amplification was evaluated by FISH analysis using the ESR1/CEP6 ratio indi-cating focal copy number alterations. Results: Focal ESR1 copy-number elevations (amplifications) were detected in 187 of 394 (47%) tumor specimens, and were associated with a favorable outcome: After a median follow-up of 10 years, women with intratumoral focal ESR1 amplification had a significantly longer distant recurrence-free survival [adjusted HR, 0.48; 95% confidence interval (CI), 0.26-0.91; P = 0.02] and breast cancer-specific survival (adjusted HR 0.47; 95% CI, 0.27-0.80; P = 0.01) as compared with women without ESR1 amplification. IHC ERa protein expression, evaluated by Allred score, correlated significantly with focal ESR1 amplification (P < 0.0001; x2 test), but was not prognostic by itself. Conclusions: Focal ESR1 amplification 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 tamoxifen for 5 years.