The cutoff for estrogen and progesterone receptor expression in endometrial cancer revisited: a European Network for Individualized Treatment of Endometrial Cancer collaboration study

Weelden, Willem Jan van; Reijnen, Casper; Küsters‐Vandevelde, Heidi V.N.; Bulten, Johan; Bult, Peter; Leung, Samuel; Visser, Nicole C.M.; Santacana, Marı́a; Bronsert, Peter; Hirschfeld, Marc; Colás, Eva; Reques, Armando; Mancebo, Gemma; Huvila, Jutta; Koskas, Martin; Weinberger, Vít; Bednaříková, Markéta; Hausnerová, Jitka; Snijders, Marc P.L.M.; Matías‐Guiu, Xavier; Amant, Frédéric; Krakstad, Camilla; Vijver, Koen Van de; McAlpine, Jessica; Pijnenborg, Johanna M.A.

doi:10.1016/j.humpath.2020.12.003

Cited by 25 publications

(28 citation statements)

References 36 publications

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“…Aside from its predictive relevance, PR IHC expression is also a strong prognostic marker potentially impacting response to hormonal therapy and outcome in cases with PR-negative disease. 19,20 In our study, 50% of tamoxifen and 25% of aromatase inhibitor users had a PR IHC expression of 10%. Therefore, a larger cohort of patients with nonprogestin hormonal drugs is necessary to validate the role of PR IHC expression and ERPAS.…”

Section: Commentsupporting

confidence: 44%

“…and J.B.) with experience in ER and PR scoring. 19 Scoring was performed blinded for clinical data. In case of disagreement, the final score was decided in a consensus meeting.…”

Section: Immunohistochemical Staining and Scoringmentioning

confidence: 99%

“…15e18 Estrogen receptor alpha (ER) and progesterone receptor (PR), as evaluated with immunohistochemical expression (IHC), are currently used biomarkers for prognosis and response to hormonal therapy with superior outcome for ER or PR positive ECs compared to ER or PR negative ECs. 10,11,19,20 Contrary to breast cancer, there is no uniform cutoff value for ER and PR IHC expressions. In clinical practice, 10% of tumor-positive nuclei is a frequently used cutoff value for prognosis with consistent relations with disease-specific and disease-free survival.…”

Section: Introductionmentioning

confidence: 99%

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

Weelden¹,

Lalisang

Bulten

et al. 2021

American Journal of Obstetrics and Gynecology

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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 reactionebased messenger RNA model to measure the activity of estrogen receptorerelated 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, 20.9e43.7) for an estrogen receptor expression of >50% and 50.0% (95% confidence interval, 35.2e64.8) for a progesterone receptor expression of >50%. Clinical benefit rate was 56.9% for an estrogen receptor expression of >50% (95% confidence interval, 44.9e68.9) and 75.0% (95% confidence interval, 62.2e87.8) 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, 42.1e73.1). After 2 years of follow-up, 34.3% of cases (95% confidence interval, 20e48) with a progesterone receptor expression of >50% and 35.8% of cases (95% confidence interval, 20e52) 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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Section: Commentsupporting

confidence: 44%

“…and J.B.) with experience in ER and PR scoring. 19 Scoring was performed blinded for clinical data. In case of disagreement, the final score was decided in a consensus meeting.…”

Section: Immunohistochemical Staining and Scoringmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Weelden¹,

Lalisang

Bulten

et al. 2021

American Journal of Obstetrics and Gynecology

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“…The expression of ER/PR was studied in relation to the TCGA groups and although predictive for outcome in the univariate analysis, overruled by the ProMisE subtypes in multivariate analysis [ 97 ]. Yet, cut-off values for ER/PR of 5% and 1% were used, that might have underestimated their prognostic value as Weelden, et al demonstrated the relevance of classification EC based on ER/PR into: high (0–10%), intermediate (20–80%), and low-risk (90–100%) groups [ 98 ]. A CTNNB1 mutation was more frequently detected in grade 1 and 2 EEC, though associated to a worse recurrence free survival.…”

Section: Knowledge Gaps and Possible Solutionsmentioning

confidence: 99%

Risk Stratification of Endometrial Cancer Patients: FIGO Stage, Biomarkers and Molecular Classification

Kasius¹,

Pijnenborg

Lindemann

et al. 2021

Cancers

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Endometrial cancer (EC) is the most common gynaecologic malignancy in developed countries. The main challenge in EC management is to correctly estimate the risk of metastases at diagnosis and the risk to develop recurrences in the future. Risk stratification determines the need for surgical staging and adjuvant treatment. Detection of occult, microscopic metastases upstages patients, provides important prognostic information and guides adjuvant treatment. The molecular classification subdivides EC into four prognostic subgroups: POLE ultramutated; mismatch repair deficient (MMRd); nonspecific molecular profile (NSMP); and TP53 mutated (p53abn). How surgical staging should be adjusted based on preoperative molecular profiling is currently unknown. Moreover, little is known whether and how other known prognostic biomarkers affect prognosis prediction independent of or in addition to these molecular subgroups. This review summarizes the factors incorporated in surgical staging (i.e., peritoneal washing, lymph node dissection, omentectomy and peritoneal biopsies), and its impact on prognosis and adjuvant treatment decisions in an era of molecular classification of EC. Moreover, the relation between FIGO stage and molecular classification is evaluated including the current gaps in knowledge and future perspectives.

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“…Recognizing that hormonal receptors’ cut-offs (10%) are based on breast cancer data and, therefore, a potential source of bias, we sought to apply newer, more accurate cut-offs previously published by our group [ 11 ] pursuant to the recently published European Network for Individualized Treatment of Endometrial Cancer (ENITEC) collaboration study. The authors divided endometrial cancer into three prognostic groups based on ER/PR expression: high-risk (0–10%), intermediate-risk (20–80%) and low-risk (90–100%) [ 33 ]. Even after employing alternative cut-offs for ER, PR, and L1CAM of 88%, 78%, and 4% respectively, we did not record any significant difference between symptomatic and asymptomatic groups.…”

Section: Discussionmentioning

confidence: 99%

Tumor Characteristic Variations between Symptomatic and Asymptomatic Endometrial Cancer

et al. 2021

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Endometrial cancer is the most common gynecologic malignancy in Europe and usually diagnosed in its initial stage owing to early symptoms of abnormal bleeding. There is no population screening for this disease, although it can sometimes be accidentally diagnosed in asymptomatic patients. Our study aims to determine differences in clinical and tumor characteristics between an asymptomatic and symptomatic group of patients. This unicentric prospective observational study took place in University Hospital Brno between January 2016 and December 2019. A total of 264 patients met inclusion criteria (26% asymptomatic, 74% with reported symptoms). We did not find a statistically significant difference in clinical characteristics (menopausal status, parity, age, BMI, and serum level of CA 125) between groups. According to ultrasound examination, bleeding tumors were larger (19.5 vs. 12.7 mm, p ≤ 0.001). Definitive histology results indicated more frequent lymphovascular space invasion (p < 0.001), along with deep myometrial (p = 0.001) and cervical (p = 0.002) invasion. There was no difference in advanced stages of the tumor. We did not substantiate statistically significant difference in immunohistochemical profile (estrogen and progesterone receptors, L1 cell adhesion molecule, tumor protein p53), which is relevant for tumor recurrence risk and survival capacity. Our conclusions affirmed that bleeding occurs more often among patients with local tumor invasion into the myometrium and cervical stroma. Final International Federation of Gynecology and Obstetrics (FIGO) stage, histology, and immunohistochemical characteristics do not significantly affect symptom appearance.

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The cutoff for estrogen and progesterone receptor expression in endometrial cancer revisited: a European Network for Individualized Treatment of Endometrial Cancer collaboration study

Cited by 25 publications

References 36 publications

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

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

Risk Stratification of Endometrial Cancer Patients: FIGO Stage, Biomarkers and Molecular Classification

Tumor Characteristic Variations between Symptomatic and Asymptomatic Endometrial Cancer

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