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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

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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, Vol. 28, No. 18, 15.09.2022, p. 4112-4120.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Singer, CF, Holst, F, Steurer, S, Burandt, EC, Lax, SF, Jakesz, R, Rudas, M, Stöger, H, Greil, R, Sauter, G, Filipits, M, Simon, R, Gnant, M & ABCSG 2022, '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, vol. 28, no. 18, pp. 4112-4120. https://doi.org/10.1158/1078-0432.CCR-21-4328

APA

Singer, C. F., Holst, F., Steurer, S., Burandt, E. C., Lax, S. F., Jakesz, R., Rudas, M., Stöger, H., Greil, R., Sauter, G., Filipits, M., Simon, R., Gnant, M., & ABCSG (2022). 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, 28(18), 4112-4120. https://doi.org/10.1158/1078-0432.CCR-21-4328

Vancouver

Singer CF, Holst F, Steurer S, Burandt EC, Lax SF, Jakesz R et al. 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 Sep 15;28(18):4112-4120. https://doi.org/10.1158/1078-0432.CCR-21-4328

Bibtex

@article{f341481e0ab44be0903dbcea85c8d874,
title = "Estrogen Receptor Alpha Gene Amplification Is an Independent Predictor of Long-Term Outcome in Postmenopausal Patients with Endocrine-Responsive Early Breast Cancer",
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 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.",
keywords = "Antineoplastic Agents, Hormonal/therapeutic use, Breast Neoplasms/drug therapy, Endocrine Gland Neoplasms/genetics, Estrogen Receptor alpha/genetics, Female, Gene Amplification, Humans, Postmenopause/genetics, Prognosis, Prospective Studies, Tamoxifen/therapeutic use",
author = "Singer, {Christian F} and Frederik Holst and Stefan Steurer and Burandt, {Eike C} and Lax, {Sigurd F} and Raimund Jakesz and Margaretha Rudas and Herbert St{\"o}ger and Richard Greil and Guido Sauter and Martin Filipits and Ronald Simon and Michael Gnant and ABCSG",
note = "{\textcopyright}2022 The Authors; Published by the American Association for Cancer Research.",
year = "2022",
month = sep,
day = "15",
doi = "10.1158/1078-0432.CCR-21-4328",
language = "English",
volume = "28",
pages = "4112--4120",
journal = "CLIN CANCER RES",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "18",

}

RIS

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 -