Impact of hormonal biomarkers on response to hormonal therapy
in advanced and recurrent endometrial cancer

WEELDEN, van W. J., R. I. LALISANG, J. BULTEN, K. LINDEMANN, H. J. VAN BEEKHUIZEN, H. TRUM, D. BOLL, H. M. J. WERNER, L. R. C. W. VAN LONKHUIJZEN, R. YIGIT, D. FORSSE, P. O. WITTEVEEN, K. GALAAL, A. VAN GINKEL, E. BIGNOTTI, Vít WEINBERGER, S. SWEEGERS, J. R. KROEP, S. CABRERA, M. P. L. M. SNIJDERS, M. A. INDA, A. G. Z. ERIKSSON, C. KRAKSTAD, A. ROMANO, A. VAN DE STOLPE and J. M. A. PIJNENBORG. Impact of hormonal biomarkers on response to hormonal therapy in advanced and recurrent endometrial cancer. American journal of obstetrics and gynecology. St. Louis: C.V. Mosby, 2021, vol. 225, No 4, p. "407.e1"-"407.e16", 16 pp. ISSN 0002-9378. Available from: https://dx.doi.org/10.1016/j.ajog.2021.05.007.

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TY  - JOUR
ID  - 1807760
AU  - Weelden, van W. J. - Lalisang, R. I. - Bulten, J. - Lindemann, K. - van Beekhuizen, H. J. - Trum, H. - Boll, D. - Werner, H. M. J. - van Lonkhuijzen, L. R. C. W. - Yigit, R. - Forsse, D. - Witteveen, P. O. - Galaal, K. - van Ginkel, A. - Bignotti, E. - Weinberger, Vít - Sweegers, S. - Kroep, J. R. - Cabrera, S. - Snijders, M. P. L. M. - Inda, M. A. - Eriksson, A. G. Z. - Krakstad, C. - Romano, A. - van de Stolpe, A. - Pijnenborg, J. M. A.
PY  - 2021
TI  - Impact of hormonal biomarkers on response to hormonal therapy in advanced and recurrent endometrial cancer
JF  - American journal of obstetrics and gynecology
VL  - 225
IS  - 4
SP  - "407.e1"-"407.e16"
EP  - "407.e1"-"407.e16"
PB  - C.V. Mosby
SN  - 00029378
KW  - aromatase inhibitors
KW  - estrogen receptor pathway activity
KW  - progesterone receptor
KW  - progestin therapy
UR  - https://www.sciencedirect.com/science/article/pii/S0002937821005548?via%3Dihub
N2  - BACKGROUND: Approximately 20% of women with endometrial cancer have advanced-stage disease or suffer from a recurrence. For these women, prognosis is poor, and palliative treatment options include hormonal therapy and chemotherapy. Lack of predictive biomarkers and suboptimal use of existing markers for response to hormonal therapy have resulted in overall limited efficacy. OBJECTIVE: This study aimed to improve the efficacy of hormonal therapy by relating immunohistochemical expression of estrogen and progesterone receptors and estrogen receptor pathway activity scores to response to hormonal therapy. STUDY DESIGN: Patients with advanced or recurrent endometrial cancer and available biopsies taken before the start of hormonal therapy were identified in 16 centers within the European Network for Individualized Treatment in Endometrial Cancer and the Dutch Gynecologic Oncology Group. Tumor tissue was analyzed for estrogen and progesterone receptor expressions and estrogen receptor pathway activity using a quantitative polymerase chain reaction-based messenger RNA model to measure the activity of estrogen receptor-related target genes in tumor RNA. The primary endpoint was response rate defined as complete and partial response using the Response Evaluation Criteria in Solid Tumors. The secondary endpoints were clinical benefit rate and progression-free survival. RESULTS: Pretreatment biopsies with sufficient endometrial cancer tissue and complete response evaluation were available in 81 of 105 eligible cases. Here, 22 of 81 patients (27.2%) with a response had estrogen and progesterone receptor expressions of >50%, resulting in a response rate of 32.3% (95% confidence interval, 20.9-43.7) for an estrogen receptor expression of >50% and 50.0% (95% confidence interval, 35.2-64.8) for a progesterone receptor expression of >50%. Clinical benefit rate was 56.9% for an estrogen receptor expression of >50% (95% confidence interval, 44.9-68.9) and 75.0% (95% confidence interval, 62.2-87.8) for a progesterone receptor expression of >50%. The application of the estrogen receptor pathway test to cases with a progesterone receptor expression of >50% resulted in a response rate of 57.6% (95% confidence interval, 42.1-73.1). After 2 years of follow-up, 34.3% of cases (95% confidence interval, 20-48) with a progesterone receptor expression of >50% and 35.8% of cases (95% confidence interval, 20-52) with an estrogen receptor pathway activity score of >15 had not progressed. CONCLUSION: The prediction of response to hormonal treatment in endometrial cancer improves substantially with a 50% cutoff level for progesterone receptor immunohistochemical expression and by applying a sequential test algorithm using progesterone receptor immunohistochemical expression and estrogen receptor pathway activity scores. However, results need to be validated in the prospective Prediction of Response to Hormonal Therapy in Advanced and Recurrent Endometrial Cancer (PROMOTE) study.
ER  -

Basic information
Original name	Impact of hormonal biomarkers on response to hormonal therapy in advanced and recurrent endometrial cancer
Authors	WEELDEN, van W. J., R. I. LALISANG, J. BULTEN, K. LINDEMANN, H. J. VAN BEEKHUIZEN, H. TRUM, D. BOLL, H. M. J. WERNER, L. R. C. W. VAN LONKHUIJZEN, R. YIGIT, D. FORSSE, P. O. WITTEVEEN, K. GALAAL, A. VAN GINKEL, E. BIGNOTTI, Vít WEINBERGER (203 Czech Republic, belonging to the institution), S. SWEEGERS, J. R. KROEP, S. CABRERA, M. P. L. M. SNIJDERS, M. A. INDA, A. G. Z. ERIKSSON, C. KRAKSTAD, A. ROMANO, A. VAN DE STOLPE and J. M. A. PIJNENBORG.
Edition	American journal of obstetrics and gynecology, St. Louis, C.V. Mosby, 2021, 0002-9378.

Other information
Original language	English
Type of outcome	Article in a journal
Field of Study	30214 Obstetrics and gynaecology
Country of publisher	United States of America
Confidentiality degree	is not subject to a state or trade secret
WWW	URL
Impact factor	Impact factor: 10.693
RIV identification code	RIV/00216224:14110/21:00123113
Organization unit	Faculty of Medicine
Doi	http://dx.doi.org/10.1016/j.ajog.2021.05.007
UT WoS	000720311600011
Keywords in English	aromatase inhibitors; estrogen receptor pathway activity; progesterone receptor; progestin therapy
Tags	14110411, rivok
Tags	International impact, Reviewed
Changed by	Changed by: Mgr. Tereza Miškechová, učo 341652. Changed: 6/12/2021 08:41.

Abstract

BACKGROUND: Approximately 20% of women with endometrial cancer have advanced-stage disease or suffer from a recurrence. For these women, prognosis is poor, and palliative treatment options include hormonal therapy and chemotherapy. Lack of predictive biomarkers and suboptimal use of existing markers for response to hormonal therapy have resulted in overall limited efficacy. OBJECTIVE: This study aimed to improve the efficacy of hormonal therapy by relating immunohistochemical expression of estrogen and progesterone receptors and estrogen receptor pathway activity scores to response to hormonal therapy. STUDY DESIGN: Patients with advanced or recurrent endometrial cancer and available biopsies taken before the start of hormonal therapy were identified in 16 centers within the European Network for Individualized Treatment in Endometrial Cancer and the Dutch Gynecologic Oncology Group. Tumor tissue was analyzed for estrogen and progesterone receptor expressions and estrogen receptor pathway activity using a quantitative polymerase chain reaction-based messenger RNA model to measure the activity of estrogen receptor-related target genes in tumor RNA. The primary endpoint was response rate defined as complete and partial response using the Response Evaluation Criteria in Solid Tumors. The secondary endpoints were clinical benefit rate and progression-free survival. RESULTS: Pretreatment biopsies with sufficient endometrial cancer tissue and complete response evaluation were available in 81 of 105 eligible cases. Here, 22 of 81 patients (27.2%) with a response had estrogen and progesterone receptor expressions of >50%, resulting in a response rate of 32.3% (95% confidence interval, 20.9-43.7) for an estrogen receptor expression of >50% and 50.0% (95% confidence interval, 35.2-64.8) for a progesterone receptor expression of >50%. Clinical benefit rate was 56.9% for an estrogen receptor expression of >50% (95% confidence interval, 44.9-68.9) and 75.0% (95% confidence interval, 62.2-87.8) for a progesterone receptor expression of >50%. The application of the estrogen receptor pathway test to cases with a progesterone receptor expression of >50% resulted in a response rate of 57.6% (95% confidence interval, 42.1-73.1). After 2 years of follow-up, 34.3% of cases (95% confidence interval, 20-48) with a progesterone receptor expression of >50% and 35.8% of cases (95% confidence interval, 20-52) with an estrogen receptor pathway activity score of >15 had not progressed. CONCLUSION: The prediction of response to hormonal treatment in endometrial cancer improves substantially with a 50% cutoff level for progesterone receptor immunohistochemical expression and by applying a sequential test algorithm using progesterone receptor immunohistochemical expression and estrogen receptor pathway activity scores. However, results need to be validated in the prospective Prediction of Response to Hormonal Therapy in Advanced and Recurrent Endometrial Cancer (PROMOTE) study.

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Impact of hormonal biomarkers on response to hormonal therapy in advanced and recurrent endometrial ...

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