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dc.contributor.authorvan Weelden, Willem Jan
dc.contributor.authorLalisang, Roy I
dc.contributor.authorBulten, Johan
dc.contributor.authorLindemann, Kristina Yvonne Kathe
dc.contributor.authorvan Beekhuizen, Heleen J.
dc.contributor.authorTrum, Hans
dc.contributor.authorBoll, Dorry
dc.contributor.authorWerner, Henrica Maria Johanna
dc.contributor.authorLonkhuijzen, Luc R C W van
dc.contributor.authorYigit, Refika
dc.contributor.authorForsse, David
dc.contributor.authorWitteveen, Petronella O
dc.contributor.authorGalaal, Khadra
dc.contributor.authorvan Ginkel, Alexandra
dc.contributor.authorBignotti, Eliana
dc.contributor.authorWeinberger, Vit
dc.contributor.authorSweegers, Sanne
dc.contributor.authorKroep, Judith R.
dc.contributor.authorCabrera, Silvia
dc.contributor.authorSnijders, Marc P.L.M.
dc.contributor.authorInda, Márcia A
dc.contributor.authorEriksson, Ane Gerda Zahl
dc.contributor.authorKrakstad, Camilla
dc.contributor.authorRomano, Andrea
dc.contributor.authorStolpe, Anja van de
dc.contributor.authorPijnenborg, Johanna M.A.
dc.description.abstractBackground 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.en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.titleImpact of hormonal biomarkers on response to hormonal therapy in advanced and recurrent endometrial canceren_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.source.journalAmerican Journal of Obstetrics and Gynecologyen_US
dc.identifier.citationAmerican Journal of Obstetrics and Gynecology. 2021, 225 (4), 407.e1-407.e16.en_US

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Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal
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