Diagnostic Assessment of Tamoxifen-Associated Endometrial Pathology: A Narrative Review of Biomarkers, Risk Models, and Translational Gaps

In tamoxifen-related endometrial alterations, a challenge arises due to the similarity between clinically significant diseases and both benign proliferation and benign polyps. This narrative review examines the clinical assessment, imaging, tissue sampling, biomarkers, and prediction models for women taking tamoxifen. We searched PubMed/MEDLINE and selected articles from reference lists up to August 2026, focusing on human studies reporting diagnostic performance, biomarkers, sampling limitations, or clinical prediction. Evidence was divided into three groups: tamoxifen-specific clinical studies, external studies of endometrial cancer, and mechanistic investigations; however, the heterogeneous populations and endpoints prevented pooled accuracy estimates. Although thickening of the endometrium is associated with an increased risk of abnormal bleeding, the finding when there is no abnormal bleeding is not significant enough to warrant routine surveillance of asymptomatic users. Representative histopathology remains the key, especially if hysteroscopy is used for sampling, particularly if the area is focal or if a diagnosis is not reached. These tissue markers primarily reflect the biology of exposure and show promise in methylation, cytology, serum-marker, and prediction studies, mostly in populations that are not tamoxifen-validated. Thus, reported discrimination does not provide sufficient reassurance to exclude atypical hyperplasia or carcinoma in tamoxifen users. The priorities are prospective validation in well-defined symptomatic patient groups, independent validation of locked assays or models against clinical baseline, and a focus on missed significant disease, avoided procedures, and patient outcomes. The current evidence favors a cautious diagnostic evaluation and does not define a biomarker-based screening or surveillance approach for women taking tamoxifen.