Britt K. Erickson, Howard Bailey, Rebecca C. Arend, Dina El-Rayes, Mahmoud A. Khalifa, Amy Skubitz, Kristin Boylan, Andrew C. Nelson, Anna Burton, Bharat Thyagarajan, Thomas Havighurst, KyungMann Kim, Eileen Dimond, Katina DeShong, Brandy Heckman-Stoddard, Goli Samimi, Eva Szabo, Lisa Barroilhet
{"title":"每日依西美坦治疗子宫内膜上皮内瘤变或低级别子宫内膜癌的初步研究","authors":"Britt K. Erickson, Howard Bailey, Rebecca C. Arend, Dina El-Rayes, Mahmoud A. Khalifa, Amy Skubitz, Kristin Boylan, Andrew C. Nelson, Anna Burton, Bharat Thyagarajan, Thomas Havighurst, KyungMann Kim, Eileen Dimond, Katina DeShong, Brandy Heckman-Stoddard, Goli Samimi, Eva Szabo, Lisa Barroilhet","doi":"10.1158/1078-0432.ccr-25-1878","DOIUrl":null,"url":null,"abstract":"Objective: To evaluate exemestane, an aromatase inhibitor, as a preventive intervention for endometrial cancer. Methods: This is a multi-center, single-arm, ‘window of opportunity’ pilot study of exemestane (25 mg daily for 21-42 days) in postmenopausal individuals undergoing hysterectomy for endometrial intraepithelial neoplasia (EIN) or low-grade endometrial cancer (EC). The primary objective is to determine change in proliferation, measured by Ki-67 expression, in pre- and post-treatment endometrial tissues specimens. Secondary outcomes include measurement of circulating serum estradiol and progesterone levels, pathologic response, tissue biomarkers, safety, and adverse effects. Results: Forty participants were accrued to the study. Preoperative diagnoses included EIN (n=11, 27.5%), grade 1 EC (n=26, 65%), and grade 2 EC (n=3, 7.5%). Median Ki-67 score decreased from 40.7% [IQR (33.9, 50.3)] at baseline to 18.1% [IQR (8.8, 31.8)] at surgery, representing a median absolute change of 20.4% [IQR (-29.9, -6.7), p<0.001]. In a matched historical control cohort, participants also had a decrease in Ki-67 score with a median absolute change from baseline of -6.7% [IQR (-12.7, -1.3), p 0.001]. However, the decrease in Ki-67 was greater in the study participants than the historic controls, with a median difference between the groups of -13.4% [IQR (-23.3, 6.9), p ]. Both tissue ER and PR expression declined significantly with exemestane treatment (p<0.001). However, serum estradiol levels did not change between baseline and post-treatment (p=0.16). Conclusion: In this pilot study, exemestane demonstrated anti-proliferative effects in endometrial intraepithelial neoplasia and low-grade endometrial cancer. This agent warrants further evaluation for the prevention of endometrial cancer.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"8 1","pages":""},"PeriodicalIF":10.2000,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pilot Study of Daily Exemestane in Women with Endometrial Intraepithelial Neoplasia or Low Grade Endometrial Cancer\",\"authors\":\"Britt K. Erickson, Howard Bailey, Rebecca C. Arend, Dina El-Rayes, Mahmoud A. Khalifa, Amy Skubitz, Kristin Boylan, Andrew C. Nelson, Anna Burton, Bharat Thyagarajan, Thomas Havighurst, KyungMann Kim, Eileen Dimond, Katina DeShong, Brandy Heckman-Stoddard, Goli Samimi, Eva Szabo, Lisa Barroilhet\",\"doi\":\"10.1158/1078-0432.ccr-25-1878\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Objective: To evaluate exemestane, an aromatase inhibitor, as a preventive intervention for endometrial cancer. Methods: This is a multi-center, single-arm, ‘window of opportunity’ pilot study of exemestane (25 mg daily for 21-42 days) in postmenopausal individuals undergoing hysterectomy for endometrial intraepithelial neoplasia (EIN) or low-grade endometrial cancer (EC). The primary objective is to determine change in proliferation, measured by Ki-67 expression, in pre- and post-treatment endometrial tissues specimens. Secondary outcomes include measurement of circulating serum estradiol and progesterone levels, pathologic response, tissue biomarkers, safety, and adverse effects. Results: Forty participants were accrued to the study. Preoperative diagnoses included EIN (n=11, 27.5%), grade 1 EC (n=26, 65%), and grade 2 EC (n=3, 7.5%). Median Ki-67 score decreased from 40.7% [IQR (33.9, 50.3)] at baseline to 18.1% [IQR (8.8, 31.8)] at surgery, representing a median absolute change of 20.4% [IQR (-29.9, -6.7), p<0.001]. In a matched historical control cohort, participants also had a decrease in Ki-67 score with a median absolute change from baseline of -6.7% [IQR (-12.7, -1.3), p 0.001]. However, the decrease in Ki-67 was greater in the study participants than the historic controls, with a median difference between the groups of -13.4% [IQR (-23.3, 6.9), p ]. Both tissue ER and PR expression declined significantly with exemestane treatment (p<0.001). However, serum estradiol levels did not change between baseline and post-treatment (p=0.16). Conclusion: In this pilot study, exemestane demonstrated anti-proliferative effects in endometrial intraepithelial neoplasia and low-grade endometrial cancer. This agent warrants further evaluation for the prevention of endometrial cancer.\",\"PeriodicalId\":10279,\"journal\":{\"name\":\"Clinical Cancer Research\",\"volume\":\"8 1\",\"pages\":\"\"},\"PeriodicalIF\":10.2000,\"publicationDate\":\"2025-10-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Cancer Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1158/1078-0432.ccr-25-1878\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1158/1078-0432.ccr-25-1878","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Pilot Study of Daily Exemestane in Women with Endometrial Intraepithelial Neoplasia or Low Grade Endometrial Cancer
Objective: To evaluate exemestane, an aromatase inhibitor, as a preventive intervention for endometrial cancer. Methods: This is a multi-center, single-arm, ‘window of opportunity’ pilot study of exemestane (25 mg daily for 21-42 days) in postmenopausal individuals undergoing hysterectomy for endometrial intraepithelial neoplasia (EIN) or low-grade endometrial cancer (EC). The primary objective is to determine change in proliferation, measured by Ki-67 expression, in pre- and post-treatment endometrial tissues specimens. Secondary outcomes include measurement of circulating serum estradiol and progesterone levels, pathologic response, tissue biomarkers, safety, and adverse effects. Results: Forty participants were accrued to the study. Preoperative diagnoses included EIN (n=11, 27.5%), grade 1 EC (n=26, 65%), and grade 2 EC (n=3, 7.5%). Median Ki-67 score decreased from 40.7% [IQR (33.9, 50.3)] at baseline to 18.1% [IQR (8.8, 31.8)] at surgery, representing a median absolute change of 20.4% [IQR (-29.9, -6.7), p<0.001]. In a matched historical control cohort, participants also had a decrease in Ki-67 score with a median absolute change from baseline of -6.7% [IQR (-12.7, -1.3), p 0.001]. However, the decrease in Ki-67 was greater in the study participants than the historic controls, with a median difference between the groups of -13.4% [IQR (-23.3, 6.9), p ]. Both tissue ER and PR expression declined significantly with exemestane treatment (p<0.001). However, serum estradiol levels did not change between baseline and post-treatment (p=0.16). Conclusion: In this pilot study, exemestane demonstrated anti-proliferative effects in endometrial intraepithelial neoplasia and low-grade endometrial cancer. This agent warrants further evaluation for the prevention of endometrial cancer.
期刊介绍:
Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.