Abstract
Tamoxifen, a selective estrogen receptor modulator (SERM), is commonly prescribed in hormone receptor-positive breast cancer. While effective in reducing recurrence and mortality, tamoxifen is associated with weight gain in a significant proportion of patients. This weight gain complicates survivorship care, particularly given obesity’s association with recurrence risk and all-cause mortality. Although lifestyle modification remains the standard of care for weight management, many breast cancer survivors struggle to achieve sufficient results with behavioral interventions alone. Current guidelines from oncology and obesity societies provide limited, nonspecific direction regarding pharmacologic weight management for tamoxifen-treated patients. Medication classes including GLP-1 receptor agonists, tirzepatide, phentermine-topiramate, bupropion-naltrexone, and orlistat are reviewed with attention to efficacy, safety, potential interactions, and tamoxifen-specific considerations. Practical monitoring strategies and prescribing considerations are provided to support oncology practitioners. This narrative review summarizes available evidence on tamoxifen-associated weight gain and outlines considerations for the use of anti-obesity medications in this population.
References
American Cancer Society. (2024). Nutrition and physical activity guidelines for cancer survivors. https://www.cancer.org/cancer/risk-prevention/diet-physical-activity/acs-guidelines-nutrition-physical-activity-cancer-prevention.html
American Cancer Society. (2026). Key Statistics for Breast Cancer. https://www.cancer.org/cancer/types/breast-cancer/about/how-common-is-breast-cancer.html
Apovian, C. M., Aronne, L. J., Bessesen, D. H., McDonnell, M. E., Murad, M. H., Pagotto, U., & Ryan, D. H. (2015). Pharmacological management of obesity: An endocrine society clinical practice guideline. The Journal of Clinical Endocrinology & Metabolism, 100(2), 342–362. https://doi.org/10.1210/jc.2014-3415
Bekes, I., & Huober, J. (2023). Extended adjuvant endocrine therapy in early breast cancer patients-review and perspectives. Cancers, 15(16), 4190. https://doi.org/10.3390/cancers15164190
Burstein, H. J., Lacchetti, C., Anderson, H., Buchholz, T. A., Davidson, N. E., Gelmon, K. A., Giordano, S. H., Hudis, C. A., Solky, A. J., Stearns, V., Winer, E. P., & Griggs, J. J. (2019). Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: ASCO clinical practice guideline focused update. Journal of Clinical Oncology, 37(5), 423–438. https://doi.org/10.1200/JCO.18.01160
Drugs.com. (2025). Tamoxifen side effects. https://www.drugs.com/sfx/tamoxifen-side-effects.html
Gadde, K. M., Allison, D. B., Ryan, D. H., Peterson, C. A., Troupin, B., Schwiers, M. L., & Day, W. W. (2011). Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): A randomized, placebo-controlled, phase 3 trial. The Lancet, 377(9774), 1341–1352. https://doi.org/10.1016/S0140-6736(11)60205-5
Ginzac, A., Thivat, É., Mouret-Reynier, M.-A., Dubray-Longeras, P., Van Praagh, I., Passildas, J., Abrial, C., Kwiatkowski, F., Boirie, Y., Duclos, M., Morio, B., Gadea, É., & Durando, X. (2018). Weight evolution during endocrine therapy for breast cancer in postmenopausal patients: Effect of initial fat mass percentage and previous adjuvant treatments. Clinical Breast Cancer, 18(5), e1093–e1102. https://doi.org/10.1016/j.clbc.2017.12.008
Jastreboff, A. M., Aronne, L. J., Ahmad, N. N., Wharton, S., Connery, L., Alves, B.,...Kushner, R. F. (2022). Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine, 387(3), 205–216. https://doi.org/10.1056/NEJMoa2206038
Klöting, N., Kern, M., Moruzzi, M., Kovacs, P., Chakaroun, R., Schön, M. R., & Blüher, M. (2020). Tamoxifen treatment causes early hepatic insulin resistance. Acta Diabetologica, 57(4), 495–498. https://doi.org/10.1007/s00592-019-01468-6
Ligibel, J. A., Bohlke, K., May, A. M., Clinton, S. K., Demark-Wahnefried, W., Gilchrist, S. C., Irwin, M. L., Late, M., Mansfield, S., Marshall, T. F., Meyerhardt, J. A., Thomson, C. A., Wood, W. A., & Alfano, C. M. (2022). Exercise, diet, and weight management during cancer treatment: ASCO guideline. Journal of Clinical Oncology, 40(22), 2491–2507. https://doi.org/10.1200/JCO.22.00687
Nagendra, L., Bg, H., Sharma, M., & Dutta, D. (2023). Semaglutide and cancer: A systematic review and meta-analysis. Diabetes & Metabolic Syndrome, 17(9), 102834. https://doi.org/10.1016/j.dsx.2023.102834
Nyrop, K. A., O’Hare, E. A., Teal, R., Stein, K., Muss, H. B., & Charlot, M. (2021). Person-centered communication about weight and weight management: Focus group discussions in a diverse sample of women with non-metastatic breast cancer and obesity. Cancer, 127(22), 4266–4276. https://doi.org/10.1002/cncr.33843
Pi-Sunyer, X., Astrup, A., Fujioka, K., Greenway, F., Halpern, A., Krempf, M., Lau, D. C., le Roux, C. W., Violante Ortiz, R., Jensen, C. B., Wilding, J. P., & SCALE Obesity and Prediabetes NN8022-1839 Study Group. (2015). A randomized, controlled trial of 3.0 mg of liraglutide in weight management. The New England Journal of Medicine, 373(1), 11–22. https://doi.org/10.1056/NEJMoa1411892
Raghavendra, A., Sinha, A. K., Valle-Goffin, J., Shen, Y., Tripathy, D., & Barcenas, C. H. (2018). Determinants of weight gain during adjuvant endocrine therapy and association of such weight gain with recurrence in long-term breast cancer survivors. Clinical Breast Cancer, 18(1), e7–e13. https://doi.org/10.1016/j.clbc.2017.11.006
Rock, C. L., Thomson, C. A., Sullivan, K. R., Howe, C. L., Kushi, L. H., Caan, B. J., Neuhouser, M. L., Bandera, E. V., Wang, Y., Robien, K., Basen-Engquist, K. M., Brown, J. C., Courneya, K. S., Crane, T. E., Garcia, D. O., Grant, B. L., Hamilton, K. K., Hartman, S. J., Kenfield, S. A., Martinez, M. E.,…McCullough, M. L. (2022). American Cancer Society nutrition and physical activity guideline for cancer survivors. CA: A Cancer Journal for Clinicians, 72(3), 230–262. https://doi.org/10.3322/caac.21719
Rubino, D. M., Greenway, F. L., Khalid, U., O’Neil, P. M., Rosenstock, J., Sørrig, R., Wadden, T. A., Wizert, A., Garvey, W. T., & STEP 8 Investigators (2022). Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: The STEP 8 randomized clinical trial. JAMA, 327(2), 138–150. https://doi.org/10.1001/jama.2021.23619
Tondt, J., Freshwater, M., Christensen, S., Iliakova, M., Weaver, E., Benson-Davies, S., Younglove, C., Afreen, S., Karjoo, S., Khan, N., Pennings, N., Thiara, D., & Whittle, C. (2023). Obesity algorithm eBook. Obesity Medicine Association. https://obesitymedicine.org/resources/obesity-algorithm/
U.S. Food and Drug Administration. (2023). FDA approves new medication Zepbound for chronic weight management. https://www.fda.gov/news-events/press-announcements/fda-approves-new-medication-chronic-weight-management
Uhelski, A.-C. R., Blackford, A. L., Sheng, J. Y., Snyder, C., Lehman, J., Visvanathan, K., Lim, D., Stearns, V., & Smith, K. L. (2024). Factors associated with weight gain in pre- and post-menopausal women receiving adjuvant endocrine therapy for breast cancer. Journal of Cancer Survivorship, 18(3), 1683–1696. https://doi.org/10.1007/s11764-023-01408-y
Wang, L., Xu, R., Kaelber, D. C., & Berger, N. A. (2024). Glucagon-like peptide 1 receptor agonists and 13 obesity-associated cancers in patients with type 2 diabetes. JAMA Network Open, 7(7), e2421305. https://doi.org/10.1001/jamanetworkopen.2024.21305
Williams, E., Rudowitz, R., & Bell, C. (2024). Medicaid coverage of and spending on GLP-1s. KFF. https://www.kff.org/medicaid/medicaid-coverage-of-and-spending-on-glp-1s/
Zhu, J., Zhou, Y., Jin, B., & Shu, J. (2023). Role of estrogen in the regulation of central and peripheral energy homeostasis: From a menopausal perspective. Therapeutic Advances in Endocrinology and Metabolism, 14, 20420188231199359. https://doi.org/10.1177/20420188231199359