{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T05:16:49Z","timestamp":1764393409350,"version":"3.46.0"},"reference-count":35,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002635","name":"Inha University","doi-asserted-by":"crossref","award":["74980"],"award-info":[{"award-number":["74980"]}],"id":[{"id":"10.13039\/501100002635","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: The incidence of endometrial cancer (EC) is rising globally across all age groups. Endometrial intraepithelial neoplasia (EIN) is a premalignant lesion that may progress to EC if untreated. A clinical model is needed to efficiently identify women requiring prompt evaluation while avoiding unnecessary invasive procedures. Obesity is a major risk factor, but whether Asian women require a lower body mass index (BMI) cutoff than the World Health Organization (WHO) definition remains debated. This study aimed to develop a multivariable risk prediction model to guide biopsy decisions and determine an appropriate BMI cutoff for predicting EIN\/EC risk among Asian women. Methods: This study retrospectively reviewed 1192 women aged \u226518 years who underwent hysteroscopy between 2010 and 2023 at a tertiary hospital. Candidate predictors included patient age, parity, BMI, postmenopausal status, symptom of abnormal uterine bleeding (AUB), diabetes mellitus, hypertension, polycystic ovary syndrome (PCOS), use of oral contraceptives, intrauterine devices, or menopausal hormone therapy, tamoxifen treatment, presence of multiple polyps, and endometrial thickness (EMT) measured by transvaginal ultrasonography. Multivariable logistic regression with stepwise selection identified independent predictors, and model stability and calibration were assessed using 1000 bootstrap resamples. Results: EIN\/EC was diagnosed in 55 patients (4.6%). Six independent predictors were identified: postmenopausal status (adjusted odds ratio [aOR] 5.93, 95% CI 2.92\u201312.04), AUB (aOR 4.07, 1.51\u201310.97), multiple polyps (aOR 2.49, 1.33\u20134.66), PCOS (aOR 2.37, 1.08\u20135.22), BMI (aOR 1.13 per kg\/m2; 1.84 per +5 kg\/m2), and EMT (aOR 1.07 per mm, 1.02\u20131.11). When using categorical cutoffs, Obese II (BMI \u2265 30 kg\/m2) and markedly increased EMT (\u226520 mm) remained significant. Predicted probabilities ranged from 0.3% with no risk factors to 90.9% with all six risk factors present. The final model demonstrated good discrimination (AUC 0.79, 95% CI 0.73\u20130.86) and excellent calibration on bootstrap validation (mean absolute error 0.005). Conclusions: This six-factor clinical model stratifies individual EIN\/EC risk using readily available variables and may guide timely, risk-based biopsy decisions by identifying high-risk patients while minimizing unnecessary procedures in low-risk cases. BMI \u2265 30 kg\/m2 (WHO obesity threshold) was confirmed as a meaningful cutoff, but external validation is warranted to confirm its generalizability and clinical applicability.<\/jats:p>","DOI":"10.3390\/cancers17233809","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T16:31:52Z","timestamp":1764261112000},"page":"3809","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["When Should We Biopsy? A Risk Factor-Based Predictive Model for EIN and Endometrial Cancer"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0010-4144","authenticated-orcid":false,"given":"Shina","family":"Jang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Inha University Hospital, Inha University College of Medicine, Incheon 22212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Ook","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Inha University Hospital, Inha University College of Medicine, Incheon 22212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41572-021-00324-8","article-title":"Endometrial Cancer","volume":"7","author":"Makker","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"pkad001","DOI":"10.1093\/jncics\/pkad001","article-title":"Differential trends in rising endometrial cancer incidence by age, race, and ethnicity","volume":"7","author":"Liu","year":"2023","journal-title":"JNCI Cancer Spectr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"526.e1","DOI":"10.1016\/j.ajog.2024.06.026","article-title":"Uterine cancer incidence trends and 5-year relative survival by race\/ethnicity and histology among women under 50 years","volume":"231","author":"Wijayabahu","year":"2024","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s00404-021-06380-5","article-title":"Endometrial Hyperplasia as a Risk Factor of Endometrial Cancer","volume":"306","author":"Nees","year":"2022","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Giannella, L., Grelloni, C., Bernardi, M., Cicoli, C., Lavezzo, F., Sartini, G., Natalini, L., Bordini, M., Petrini, M., and Petrucci, J. (2024). Atypical Endometrial Hyperplasia and Concurrent Cancer: A Comprehensive Overview on a Challenging Clinical Condition. Cancers, 16.","DOI":"10.3390\/cancers16050914"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Doherty, M.T., Sanni, O.B., Coleman, H.G., Cardwell, C.R., McCluggage, W.G., Quinn, D., Wylie, J., and McMenamin, \u00da.C. (2020). Concurrent and future risk of endometrial cancer in women with endometrial hyperplasia: A systematic review and meta-analysis. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0232231"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"621","DOI":"10.2188\/jea.JE20200145","article-title":"Associations of Body Mass Index, Weight Change, Physical Activity, and Sedentary Behavior with Endometrial Cancer Risk Among Japanese Women: The Japan Collaborative Cohort Study","volume":"31","author":"Miyata","year":"2021","journal-title":"J. Epidemiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1097\/CEJ.0000000000000449","article-title":"Association of BMI and height with the risk of endometrial cancer, overall and by histological subtype: A population-based prospective cohort study in Japan","volume":"28","author":"Kawachi","year":"2019","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1097\/GME.0000000000001822","article-title":"Obesity increases endometrial cancer risk in Chinese women with postmenopausal bleeding","volume":"28","author":"Liu","year":"2021","journal-title":"Menopause"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"168","DOI":"10.3892\/ol.2023.13754","article-title":"Risk of endometrial cancer in patients with polycystic ovarian syndrome: A meta-analysis","volume":"25","author":"Johnson","year":"2023","journal-title":"Oncol. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Jaya-Bodestyne, S.L., Goh, M.S., Gwan, M.C.H., Chonkar, S.P., Merchant, K., and Mathur, M. (2025). To do or not to do?\u2014Endometrial biopsy in younger women with abnormal uterine bleeding. Eur. J. Obstet. Gynecol. Reprod. Biol. X, 25.","DOI":"10.1016\/j.eurox.2025.100368"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e2332296","DOI":"10.1001\/jamanetworkopen.2023.32296","article-title":"Reproductive Factors and Endometrial Cancer Risk Among Women","volume":"6","author":"Katagiri","year":"2023","journal-title":"JAMA Netw. Open"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wang, L., Quan, S., Bai, E., and Yang, X. (2024). Analysis of clinical data of different endometrial pathological types in perimenopausal women with abnormal uterine bleeding. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1370681"},{"key":"ref_15","unstructured":"World Health Organization, International Association for the Study of Obesity, and International Obesity Task Force (2000). The Asia-Pacific Perspective: Redefining Obesity and Its Treatment, Health Communications Australia."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0140-6736(03)15268-3","article-title":"Appropriate Body-Mass Index for Asian Populations and Its Implications for Policy and Intervention Strategies","volume":"363","author":"Tan","year":"2004","journal-title":"Lancet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.bpobgyn.2015.11.012","article-title":"Abnormal Uterine Bleeding","volume":"34","author":"Whitaker","year":"2016","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"ESHRE\/ASRM Rotterdam Consensus Workshop Group (2004). Revised 2003 Consensus on Diagnostic Criteria and Long-Term Health Risks Related to Polycystic Ovary Syndrome (PCOS). Fertil. Steril., 81, 19\u201325.","DOI":"10.1016\/j.fertnstert.2003.10.004"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Liu, W., and Bai, W. (2025). Association of endometrial thickness with lesions in postmenopausal asymptomatic women: Risk factors and diagnostic thresholds. BMC Women\u2019s Health, 25.","DOI":"10.1186\/s12905-025-03641-2"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1002\/sim.7992","article-title":"Minimum Sample Size for Developing a Multivariable Prediction Model: Part II\u2014Binary and Time-to-Event Outcomes","volume":"38","author":"Riley","year":"2019","journal-title":"Stat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"m441","DOI":"10.1136\/bmj.m441","article-title":"Calculating the sample size required for developing a clinical prediction model","volume":"368","author":"Riley","year":"2020","journal-title":"BMJ"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Hazelwood, E., Sanderson, E., Tan, V.Y., Ruth, K.S., Frayling, T.M., Dimou, N., Gunter, M.J., Dossus, L., Newton, C., and Ryan, N. (2022). Identifying molecular mediators of the relationship between body mass index and endometrial cancer risk: A Mendelian randomization analysis. BMC Med., 20.","DOI":"10.1186\/s12916-022-02322-3"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S0140-6736(08)60269-X","article-title":"Body-mass index and incidence of cancer: A systematic review and meta-analysis of prospective observational studies","volume":"371","author":"Renehan","year":"2008","journal-title":"Lancet"},{"key":"ref_24","unstructured":"World Cancer Research Fund\/American Institute for Cancer Research (2018). Diet, Nutrition, Physical Activity and Endometrial Cancer, World Cancer Research Fund International."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"American College of Obstetricians and Gynecologists (2018). ACOG Committee Opinion No. 734: The Role of Transvaginal Ultraso-nography in Evaluating the Endometrium of Women with Postmenopausal Bleeding. Obstet. Gynecol., 131, 945\u2013946.","DOI":"10.1097\/AOG.0000000000002626"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.jacr.2024.11.008","article-title":"Re-evaluating Endometrial Thickness in Symptomatic Postmenopausal Patients for Excluding Cancer: Systematic Review and Meta-Analysis","volume":"22","author":"Chee","year":"2024","journal-title":"J. Am. Coll. Radiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"102831","DOI":"10.1016\/j.jogoh.2024.102831","article-title":"The optimal endometrial thickness threshold for prediction of endometrial cancer in postmenopausal women without bleeding remains uncertain\u2013Systematic review and meta-analysis","volume":"53","author":"Kaur","year":"2024","journal-title":"J. Gynecol. Obstet. Hum. Reprod."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Amiri, M., Bidhendi-Yarandi, R., Fallahzadeh, A., Marzban, Z., and Tehrani, F.R. (2022). Risk of endometrial, ovarian, and breast cancers in women with polycystic ovary syndrome: A systematic review and meta-analysis. Int. J. Reprod. Biomed., 20.","DOI":"10.18502\/ijrm.v20i11.12357"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Emanuel, R.H., Roberts, J., Docherty, P.D., Lunt, H., Campbell, R.E., and M\u00f6ller, K. (2022). A review of the hormones involved in the endocrine dysfunctions of polycystic ovary syndrome and their interactions. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1017468"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.ejogrb.2024.01.033","article-title":"The risk factors for premalignant and malignant endometrial polyps in premenopausal and postmenopausal women and trends over the past decade: A retrospective study in a single center, South Korea","volume":"295","author":"Jang","year":"2024","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.ejogrb.2022.10.018","article-title":"Does the presence of single compared to multiple endometrial polyps alter the risk of cancer in post-menopausal women?","volume":"279","author":"McGowan","year":"2022","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1007\/s00125-007-0681-5","article-title":"Diabetes mellitus and risk of endometrial cancer: A meta-analysis","volume":"50","author":"Friberg","year":"2007","journal-title":"Diabetologia"},{"key":"ref_33","first-page":"355","article-title":"Metabolic syndrome and risk of endometrial cancer in postmenopausal women: A prospective study","volume":"30","author":"Arthur","year":"2019","journal-title":"Cancer Causes Control"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1080\/13697137.2024.2376189","article-title":"Risk of endometrial malignancy in women treated for breast cancer: The BLUSH prediction model\u2014Evidence from a comprehensive multicentric retrospective cohort study","volume":"27","author":"Vitale","year":"2024","journal-title":"Climacteric"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ronsini, C., Iavarone, I., Vastarella, M.G., Della Corte, L., Andreoli, G., Bifulco, G., Cobellis, L., and De Franciscis, P. (2024). SIR-EN-New Biomarker for Identifying Patients at Risk of Endometrial Carcinoma in Abnormal Uterine Bleeding at Menopause. Cancers, 16.","DOI":"10.3390\/cancers16213567"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/23\/3809\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T05:12:33Z","timestamp":1764393153000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/23\/3809"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,27]]},"references-count":35,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["cancers17233809"],"URL":"https:\/\/doi.org\/10.3390\/cancers17233809","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2025,11,27]]}}}