Endometrial abnormalities in breast cancer patients receiving tamoxifen: a retrospective study with a cautionary note on diagnostic thresholds and verification bias
Year: 2026
Type: article
Abstract: Objective To evaluate endometrial abnormalities in breast cancer patients receiving tamoxifen and assess clinical symptoms and endometrial thickness (ET) while examining verification bias in a real-world retrospective cohort. Methods This single-center retrospective study included 120 breast cancer patients treated with tamoxifen for ≥6 months (January 2018–December 2023). Clinical, ultrasound, and pathological data were collected. Verification-bias analyses used the full cohort (n=120) with assumption-based sensitivity analysis for unverified patients and the pathology-confirmed sub-cohort (n=76) for diagnostic evaluation. Univariate and Firth-penalized multivariable logistic regression, including abnormal uterine bleeding (AUB) and ET ≥9 mm, identified predictors of non-benign lesions (atypical hyperplasia or carcinoma). Unverified patients were not assumed disease-free. Results Among 76 pathologically verified patients, the pathological abnormality rate was 81.58%, mostly polyps (36/76, 47.37%); 12 patients (15.79%) had non-benign lesions. In univariable analysis, AUB was associated with non-benign lesions (26.32% vs. 5.26%, P = 0.009). ET yielded an ROC-AUC of 0.845 (95% CI 0.752–0.938). Although 10 mm had the highest Youden index (0.563), 9 mm was selected as sensitivity-prioritized (sensitivity 83.33% vs. 75.00%). Begg-Greenes correction for the 9-mm threshold gave sensitivity 81.1%, specificity 74.9%, PPV 35.7%, and NPV 95.8% versus naive estimates of 83.33%, 71.88%, 35.7%, and 95.8%. A conservative analysis assuming all unbiopsied patients were benign yielded PPV 25.0%. In the Firth-penalized multivariable model, ET ≥ 9 mm was associated with higher odds of non-benign lesions (OR = 9.62, 95% CI 1.78–52.03, P = 0.009), although the confidence interval was wide; AUB was not statistically significant (OR = 3.85, 95% CI 0.71–20.87, P = 0.122). Conclusions ET ≥9 mm and AUB were associated with non-benign endometrial lesions, but the 9-mm threshold had a low PPV and should serve as a trigger for further work-up rather than a definitive surgical indication. Diagnostic accuracy based only on biopsied patients may be affected by selective verification bias, and dynamic ET monitoring requires prospective validation before clinical use.
Source: Frontiers in Oncology
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7225802559