Estrogen Receptor Alpha Gene Amplification Is an Independent Predictor of Long-Term Outcome in Postmenopausal Patients with Endocrine-Responsive Early Breast Cancer
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Estrogen Receptor Alpha Gene Amplification Is an Independent Predictor of Long-Term Outcome in Postmenopausal Patients with Endocrine-Responsive Early Breast Cancer. / Singer, Christian F; Holst, Frederik; Steurer, Stefan; Burandt, Eike C; Lax, Sigurd F; Jakesz, Raimund; Rudas, Margaretha; Stöger, Herbert; Greil, Richard; Sauter, Guido; Filipits, Martin; Simon, Ronald; Gnant, Michael; ABCSG.
in: CLIN CANCER RES, Jahrgang 28, Nr. 18, 15.09.2022, S. 4112-4120.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Estrogen Receptor Alpha Gene Amplification Is an Independent Predictor of Long-Term Outcome in Postmenopausal Patients with Endocrine-Responsive Early Breast Cancer
AU - Singer, Christian F
AU - Holst, Frederik
AU - Steurer, Stefan
AU - Burandt, Eike C
AU - Lax, Sigurd F
AU - Jakesz, Raimund
AU - Rudas, Margaretha
AU - Stöger, Herbert
AU - Greil, Richard
AU - Sauter, Guido
AU - Filipits, Martin
AU - Simon, Ronald
AU - Gnant, Michael
AU - ABCSG
N1 - ©2022 The Authors; Published by the American Association for Cancer Research.
PY - 2022/9/15
Y1 - 2022/9/15
N2 - 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 ERα 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 indicating 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 ERα protein expression, evaluated by Allred score, correlated significantly with focal ESR1 amplification (P < 0.0001; χ2 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.
AB - 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 ERα 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 indicating 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 ERα protein expression, evaluated by Allred score, correlated significantly with focal ESR1 amplification (P < 0.0001; χ2 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.
KW - Antineoplastic Agents, Hormonal/therapeutic use
KW - Breast Neoplasms/drug therapy
KW - Endocrine Gland Neoplasms/genetics
KW - Estrogen Receptor alpha/genetics
KW - Female
KW - Gene Amplification
KW - Humans
KW - Postmenopause/genetics
KW - Prognosis
KW - Prospective Studies
KW - Tamoxifen/therapeutic use
U2 - 10.1158/1078-0432.CCR-21-4328
DO - 10.1158/1078-0432.CCR-21-4328
M3 - SCORING: Journal article
C2 - 35920686
VL - 28
SP - 4112
EP - 4120
JO - CLIN CANCER RES
JF - CLIN CANCER RES
SN - 1078-0432
IS - 18
ER -