Tamoxifen use and risk of endometrial cancer in breast cancer patients - A systematic review and dose-response meta-analysis

Sep 24, 2026

Background: Worse prognosis of endometrial cancers (EC) in tamoxifen-treated women versus non-tamoxifen-treated women has been proposed. The association between tamoxifen treatment for breast cancer (BC) and EC risk remains controversial, with no consensus across publication results. Methods and Results: A comprehensive search in MEDLINE/PubMed, SCOPUS, and Web of Science up to April 16, 2022 was conducted, pooling risk ratios (RRs) using a random-effects model (DerSimonian and Laird). Twenty-six studies supported a direct relationship between tamoxifen and EC (RR: 2.03, 95% CI: 1.68–2.45; I2: 76%). Dose, cumulative dose, and duration showed dose–response effects; linear and non-linear analyses confirmed the findings. Age-related risk decrease was not statistically significant. Conclusion: Tamoxifen use is a significant risk factor for EC incidence in BC patients.

LanguageEnglish

CategoryHealthcare

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Abstract

Background

Methods and Results

Conclusion

Background

Mechanism and rationale

Prior studies and conflicting evidence

DOI: 10.1002/cnr2.1806 REVIE W Tamoxifen use and risk of endometrial cancer in breast cancer patients: A systematic review and dose–response meta-analysis Matin Ghanavati 1 | Yasaman Khorshidi 1 | Mahdi Shadnoush 1 | Mohammad Esmaeil Akbari 2 | Seyed Hossein Ardehali 3 | Yanin Chavarri-Guerra 4 | Atieh Akbari 2 | Regina Barragan-Carrillo 4 | Manoochehr Amin Amlashi 5 | Zeinab Javid 6 | Jamal Rahmani 2 1Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Science and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 3Department of Anesthesiology and Critical Care, Shohadaye Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran 4Department of Hemato-Oncology, Instituto Nacional de Ciencias Médicas y Nutricin Salvador Zubirán, Mexico City, Mexico 5Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran 6Department of Nutrition, Farhikhtegan hospital, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran Correspondence Jamal Rahmani, Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Email: [jrahmani@sbmu.ac.ir](jrahmani@sbmu.ac.ir) Abstract Background: Worse prognosis of endometrial cancers (EC) in tamoxifen-treated women compared to non-tamoxifen-treated women been proposed. The relationship between tamoxifen treatment of breast cancer (BC) and the risk of EC is controversial and there is no agreement between publication results on this issue (the answer to all comments provided in the page 2 of manuscript) . The aim of this study is investigation the association between tamoxifen treatment and the risk of EC in patients with BC. Methods and Results: We conducted a comprehensive search with related keywordsin MEDLINE/PubMed, SCOPUS, and Web of Science databases until April 16, 2022 . Random-effects model (DerSimonian and Laird) was used to pool risk ratios (RRs) with 95% confidence intervals (CIs) of EC. Dose, cumulative dose, and durationresponse analysis were performed in linear and non-linear states. Twenty-six studies reported a relation between tamoxifen treatment and risk of EC in patients with BC. Results showed a direct relationship between tamoxifen use and EC (RR: 2 .03, 95% CI: 1 .68–2.45; I2:76%) . By increase the age of participants, the risk of EC was decrease (coef = 􀀁 .0206), although this was not statistically significant (p = .37) . Linear dose–response model indicated a direct significant association between dose and duration use of tamoxifen and EC (dose: exe(b) = 1.019, p = .001; duration: exe (b) = 1.014, p = .001) . Non-linear dose–response analysis confirmed linear analysis. Conclusion: This study highlights that tamoxifen use is a significant risk factor related to the incidence of EC in patients with BC. KEYWOR DS breast cancer, dose–response, endometrial cancer, tamoxifen This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC. Cancer Reports. 2023;6:e1806 . [https://doi.org/10.1002/cnr2.1806](https://doi.org/10.1002/cnr2.1806) [wileyonlinelibrary.com/journal/cnr2](wileyonlinelibrary.com/journal/cnr2) 1 of 9 1 | BACKGROUND Hormone-receptor-positive breast cancer (BC) is the most frequent biologic subtype of breast malignancy, accounting around 75% of new BC diagnoses.1 Tamoxifen, an oral selective estrogen receptor modulator (SERM), is currently one of the mainstays for treating hormonereceptor-positive BC in adjuvant, especially in perimenopause women.2–4 Evidence regarding the benefit of tamoxifen extended adjuvant therapy

FAQs

What was the study aim regarding tamoxifen and endometrial cancer risk?

To investigate the association between tamoxifen treatment and the risk of endometrial cancer in patients with breast cancer.

Which databases and time cut-off were used in the systematic review?

MEDLINE/PubMed, SCOPUS, and Web of Science were searched using related keywords until April 16, 2022.

What overall effect did tamoxifen use show on endometrial cancer risk?

Tamoxifen use was directly associated with higher endometrial cancer risk (RR: 2.03, 95% CI: 1.68–2.45; I2: 76%).

How did dose and duration influence the risk of endometrial cancer?

Linear dose–response models showed significant direct associations for dose and duration of tamoxifen use, and non-linear analyses confirmed the linear results.

Sep 24, 2026

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