PMID- 32998940 OWN - NLM STAT- MEDLINE DCOM- 20220207 LR - 20220207 IS - 1940-6215 (Electronic) IS - 1940-6215 (Linking) VI - 14 IP - 2 DP - 2021 Feb TI - PROgesterone Therapy for Endometrial Cancer Prevention in Obese Women (PROTEC) Trial: A Feasibility Study. PG - 263-274 LID - 10.1158/1940-6207.CAPR-20-0248 [doi] AB - Obesity is the major etiologic driver for endometrial cancer. The levonorgestrel intrauterine system (LNG-IUS) reduces the risk of endometrial cancer and its precursor, atypical hyperplasia. We assessed feasibility and uptake of the LNG-IUS for primary prevention of endometrial cancer in high-risk women and its impact on endometrial tissue biomarkers. Women with class-III obesity [body mass index (BMI) > 40 kg/m(2)] and histologically normal endometrium were invited to participate in a clinical trial of the LNG-IUS for endometrial protection. Recruitment, successful LNG-IUS insertion, and adherence to trial procedures were recorded. We measured impact of the LNG-IUS on circulating biomarkers of endometrial cancer risk, endometrial proliferation (Ki-67, pAKT, PTEN), endometrial hormone receptor status [estrogen receptor and progesterone receptor (PR)], mental wellbeing, and menstrual function. At 6 months, women chose to keep their LNG-IUS or have it removed. In total, 103 women were approached, 54 were offered a participant information sheet, 35 agreed to participate, and 25 received a LNG-IUS. Their median age and BMI were 54 years [interquartile range (IQR) 52-57] and 47 kg/m(2) (IQR 44-51), respectively. Three women (3/35, 9%) were ineligible due to atypical hyperplasia/endometrial cancer on their baseline biopsy. The LNG-IUS was well tolerated and had a positive overall effect on bleeding patterns and mental wellbeing. The LNG-IUS was associated with endometrial morphologic change, reduced Ki-67, and PR expression, but circulating biomarkers of endometrial cancer risk were unchanged. All but one woman (96%) kept her LNG-IUS. The LNG-IUS appears to be acceptable to some women with class-III obesity for primary prevention of endometrial cancer, which could provide a strategy for a prevention trial.Prevention Relevance: Novel strategies are urgently needed to prevent the rise in endometrial cancer diagnoses predicted by escalating obesity rates. Here, we show that women with class III obesity are willing to engage in risk reduction with a levonorgestrel intrauterine system, which could provide a strategy for an endometrial cancer prevention trial. CI - (c)2020 American Association for Cancer Research. FAU - Derbyshire, Abigail E AU - Derbyshire AE AD - Division of Gynaecology, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom. FAU - Allen, Jennifer L AU - Allen JL AD - Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary's Hospital, Manchester, United Kingdom. FAU - Gittins, Matthew AU - Gittins M AD - Centre for Biostatistics, School of Health Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom. FAU - Lakhiani, Bhavna AU - Lakhiani B AD - Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary's Hospital, Manchester, United Kingdom. FAU - Bolton, James AU - Bolton J AD - Department of Histopathology, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom. FAU - Shaw, Joseph AU - Shaw J AD - Department of Histopathology, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom. FAU - Pemberton, Philip W AU - Pemberton PW AD - Department of Clinical Biochemistry, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom. FAU - Needham, Michelle AU - Needham M AD - Sleep Apnoea Service, Salford Royal Hospitals NHS Foundation Trust, Salford, United Kingdom. FAU - MacKintosh, Michelle L AU - MacKintosh ML AD - Division of Gynaecology, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom. FAU - Edmondson, Richard J AU - Edmondson RJ AUID- ORCID: 0000-0003-2553-4423 AD - Division of Gynaecology, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom. AD - Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary's Hospital, Manchester, United Kingdom. FAU - Kitchener, Henry C AU - Kitchener HC AD - Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary's Hospital, Manchester, United Kingdom. FAU - Crosbie, Emma J AU - Crosbie EJ AUID- ORCID: 0000-0003-0284-8630 AD - Division of Gynaecology, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom. emma.crosbie@manchester.ac.uk. AD - Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary's Hospital, Manchester, United Kingdom. LA - eng GR - NIHR-CS-012-009/DH_/Department of Health/United Kingdom PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200930 PL - United States TA - Cancer Prev Res (Phila) JT - Cancer prevention research (Philadelphia, Pa.) JID - 101479409 RN - 0 (Biomarkers, Tumor) RN - 5W7SIA7YZW (Levonorgestrel) SB - IM MH - Biomarkers, Tumor/blood MH - Endometrial Neoplasms/blood/diagnosis/metabolism/*prevention & control MH - Endometrium/drug effects/pathology MH - Feasibility Studies MH - Female MH - Humans MH - *Intrauterine Devices, Medicated MH - Levonorgestrel/*administration & dosage MH - Middle Aged MH - Obesity/blood/complications/*drug therapy/metabolism MH - Treatment Outcome EDAT- 2020/10/02 06:00 MHDA- 2022/02/08 06:00 CRDT- 2020/10/01 05:29 PHST- 2020/05/18 00:00 [received] PHST- 2020/08/22 00:00 [revised] PHST- 2020/09/16 00:00 [accepted] PHST- 2020/10/02 06:00 [pubmed] PHST- 2022/02/08 06:00 [medline] PHST- 2020/10/01 05:29 [entrez] AID - 1940-6207.CAPR-20-0248 [pii] AID - 10.1158/1940-6207.CAPR-20-0248 [doi] PST - ppublish SO - Cancer Prev Res (Phila). 2021 Feb;14(2):263-274. doi: 10.1158/1940-6207.CAPR-20-0248. Epub 2020 Sep 30.