This web page was created programmatically, to learn the article in its unique location you possibly can go to the hyperlink bellow: https://pmc.ncbi.nlm.nih.gov/articles/PMC13188626/and if you wish to take away this text from our website please contact us [ad_1] Abstract Tamoxifen, a selective estrogen receptor modulator (SERM), is usually prescribed in hormone receptor-positive breast most cancers. While efficient in lowering recurrence and mortality, tamoxifen is related to weight achieve in a big proportion of sufferers. This weight achieve complicates survivorship care, significantly given weight problems's affiliation with recurrence danger and all-cause mortality. Although life-style modification stays the usual of take care of weight administration, many breast most cancers survivors wrestle to attain ample outcomes with behavioral interventions alone. Current tips from oncology and weight problems societies present restricted, nonspecific course relating to pharmacologic weight administration for tamoxifen-treated sufferers. Medication lessons together with GLP-1 receptor agonists, tirzepatide, phentermine-topiramate, bupropion-naltrexone, and orlistat are reviewed with consideration to efficacy, security, potential interactions, and tamoxifen-specific issues. Practical monitoring methods and prescribing issues are offered to assist oncology practitioners. This narrative assessment summarizes accessible proof on tamoxifen-associated weight achieve and descriptions issues for using anti-obesity drugs on this inhabitants. Breast most cancers is probably the most incessantly recognized most cancers amongst ladies within the United States and continues to be one of many main causes of cancer-related mortality (ACS, 2026). In 2026, about 321,910 new circumstances of invasive breast most cancers are anticipated, with greater than 42,000 deaths (ACS, 2026). Hormone receptor-positive (HR+) breast most cancers accounts for about 70% to 80% of all breast most cancers circumstances (ACS, 2026). Tamoxifen, a selective estrogen receptor modulator, is usually prescribed as customary adjuvant endocrine remedy for premenopausal ladies with hormone receptor–constructive breast most cancers (Burstein et al., 2019). Five years of tamoxifen remedy has been proven to cut back the 15-year danger of breast most cancers recurrence by roughly 40% and the danger of dying by about 30% in contrast with no endocrine remedy (Bekes & Huober, 2023). While tamoxifen's effectiveness in lowering breast most cancers recurrence and mortality is effectively established, its long-term use has been linked to weight achieve. Recent research present that weight achieve throughout tamoxifen remedy is widespread, affecting roughly 39% to 61% of ladies, relying on menopausal standing and period of remedy. A retrospective research of 1,282 breast most cancers survivors revealed 33.7% had at the least a 5% weight achieve at 5 years (Raghavendra et al., 2018). In a research of postmenopausal ladies receiving endocrine remedy, 56% of sufferers gained weight, with a mean enhance of roughly 1.5 kg over the therapy interval (Ginzac et al., 2018). Weight achieve was extra pronounced in ladies with decrease preliminary fats mass and in those that had acquired prior chemotherapy, suggesting that baseline physique composition and therapy historical past might affect danger of weight achieve throughout endocrine remedy. In a potential cohort of 309 ladies initiating adjuvant endocrine remedy, 67% of premenopausal and 43% of postmenopausal individuals skilled clinically important weight achieve (≥ 5%) throughout therapy (Uhelski et al., 2024). Several mechanisms have been proposed to clarify tamoxifen-associated weight achieve. Tamoxifen exerts blended agonist and antagonist results relying on the tissue. Estrogen is understood to suppress urge for food by way of hypothalamic pathways; by disrupting this signaling, tamoxifen might promote elevated meals consumption or adjustments in satiety notion (Zhu et al., 2023). Tamoxifen may affect lipid metabolism and glucose homeostasis, contributing to insulin resistance and elevated fats storage (Klöting et al., 2020). These results could also be partially mediated by hepatic estrogen receptor exercise, resulting in alterations in triglyceride ranges and fats distribution (Klöting et al., 2020). Lastly, tamoxifen has been related to decreased resting vitality expenditure and lack of lean physique mass, particularly amongst postmenopausal ladies, which might result in slower metabolism and elevated fats mass, even with out important adjustments in weight loss plan or bodily exercise (Klöting et al., 2020). In breast most cancers survivors, extra adiposity is related to increased danger of recurrence, second major cancers, and all-cause mortality. Obesity can be linked to different malignancies and cardiometabolic illness, highlighting the significance of intentional weight administration in survivorship. A physique mass index (BMI) of 30 kg/m2 or increased is related to recurrence and all-cause mortality (Ligibel et al., 2022). However, BMI alone doesn't totally seize a person's danger profile. In postmenopausal ladies, adjustments in hormone ranges result in redistribution of physique fats towards the stomach, growing visceral adiposity, an vital driver of cardiometabolic danger, even when BMI stays inside the regular vary. Therefore, a extra complete evaluation is acceptable. This might embody measuring waist circumference to estimate central fats accumulation, utilizing physique composition evaluation to differentiate between lean and fats mass, and evaluating for sarcopenia, which can be accelerated by menopause and most cancers therapy. In addition to metabolic and endocrine mechanisms, tamoxifen can be related to a number of gastrointestinal signs that will affect therapy tolerance. Nausea is among the many most incessantly reported results and infrequently happens in the course of the early section of remedy (Drugs.com, 2025). Patients may describe dyspepsia, bloating, or basic stomach discomfort, and a few expertise adjustments in bowel habits akin to constipation or diarrhea (Drugs.com, 2025). Less generally, tamoxifen has been related to elevated liver enzymes or hepatic steatosis, which can be recognized via routine monitoring and will current with refined or nonspecific signs (Drugs.com, 2025). Rare circumstances of hypertriglyceridemia-induced pancreatitis have been reported (Drugs.com, 2025). CURRENT GUIDELINES Professional organizations supply steerage on weight administration in most cancers survivors, outlining when to provoke life-style interventions and think about pharmacologic therapy. The American Cancer Society's 2024 Nutrition and Physical Activity Guidelines advocate lifestyle-based methods as the first strategy to weight administration in most cancers survivors, with an emphasis on vitamin, bodily exercise, and behavioral assist. The American Society of Clinical Oncology (ASCO) recommends contemplating pharmacologic therapy for people with a BMI of 30 kg/m2 or increased, or 27 kg/m2 or increased when accompanied by obesity-related comorbidities (Ligibel et al., 2022). Similarly, the Obesity Medicine Association helps the early use of FDA-approved anti-obesity drugs for sufferers assembly these BMI thresholds, together with life-style modifications (Tondt et al., 2023). Both the ASCO and OMA emphasize that BMI ought to be used as a screening instrument as metabolic, behavioral, and social determinants modify danger at any BMI worth. Treatment targets usually embody a clinically significant weight lack of at the least 5% of complete physique weight, with the OMA recommending reassessment of pharmacologic therapy at 3 months and continuation, if at the least 5% weight reduction is achieved.PHARMACOLOGIC OPTIONS Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), akin to semaglutide 2.4 mg (Wegovy) and liraglutide 3.0 mg (Saxenda), improve insulin secretion, delay gastric emptying, and promote satiety, resulting in decreased urge for food (Table 1). In scientific trials, semaglutide has been related to common weight reductions of roughly 15% of baseline physique weight over 68 weeks, whereas liraglutide has produced reductions of roughly 5% to eight% over 56 weeks (Rubino et al., 2022). Common uncomfortable side effects embody nausea (reported in roughly 30% to 50% of sufferers), vomiting (5% to fifteen%), diarrhea (10% to twenty%), and constipation (round 10%; Rubino et al., 2022). These gastrointestinal signs might exacerbate tamoxifen-related discomfort in some sufferers. Fatigue and dehydration can happen as secondary results of persistent gastrointestinal uncomfortable side effects. Although gastrointestinal opposed results are widespread, they're usually gentle, dose-dependent, and have a tendency to enhance after the dose escalation interval. Less widespread however severe opposed occasions embody pancreatitis (lower than 1%) and gallbladder illness (roughly 1% to 2%; Rubino et al., 2022). Table 1. Comparison of Anti-Obesity Medications within the Context of Breast Cancer Survivorship and Tamoxifen Use. Medication Mechanism of motion Efficacy Cancer security issues Dosing Common uncomfortable side effects Semaglutide (Wegovy) GLP-1 receptor agonist; will increase insulin, delays gastric emptying, promotes satiety High (~15% weight reduction in STEP trials) No elevated most cancers danger reported; long-term security in survivors stays understudied Weekly injection Nausea, vomiting, diarrhea, headache Liraglutide (Saxenda) GLP-1 receptor agonist; much like semaglutide, with every day administration Moderate (~5–8% weight reduction) Higher (non-significant) incidence of breast most cancers in SCALE trial; warrants warning Daily injection GI upset, nausea, injection website reactions Tirzepatide (Zepbound) Dual GIP/GLP-1 receptor agonist; enhances insulin secretion, promotes satiety, delays gastric emptying Very excessive (~20% weight reduction in SURMOUNT trials) No direct most cancers danger noticed; lacks long-term security knowledge in hormone-sensitive populations Weekly injection Nausea, diarrhea, vomiting, fatigue Phentermine-Topiramate (Qsymia) Appetite suppressant + anticonvulsant; reduces urge for food and will increase vitality expenditure Moderate to excessive (~10% weight reduction) May enhance BP and temper disturbance; warning with cardiovascular or psychiatric comorbidities Oral, every day Dry mouth, insomnia, paresthesia, temper adjustments Bupropion-Naltrexone (Contrave) Antidepressant + opioid antagonist; reduces cravings by way of reward pathway modulation Moderate (~5–9% weight reduction) Seizure danger and GI upset; think about psychological well being standing and seizure threshold Oral, every day Nausea, constipation, headache, insomnia Orlistat (Alli, Xenical) Lipase inhibitor; blocks dietary fats absorption within the gastrointestinal tract Modest (~5% weight reduction) Minimal systemic danger; monitor for fat-soluble vitamin deficiencies and GI intolerance Oral, with meals Oily stools, flatulence, vitamin A/D/E/Ok deficiency The long-term security of GLP-1 receptor agonists in people with energetic or prior most cancers stays unclear. In the Satiety and Clinical Adiposity Liraglutide Evidence (SCALE) trial, a better incidence of breast most cancers was noticed within the liraglutide group in contrast with placebo, though this distinction was not statistically important (Pi-Sunyer et al., 2015). A scientific assessment and meta-analysis by Nagendra et al. (2023), which examined 37 randomized managed trials, discovered no statistically important enhance in total most cancers danger amongst GLP-1 customers, together with no particular affiliation with breast most cancers. However, most included trials had been of restricted period and never powered to detect malignancies. More lately, Wang et al. (2024) carried out a big retrospective, multi-center cohort research involving over 1.6 million adults with sort 2 diabetes and no prior historical past of obesity-related cancers. This research discovered no important distinction in breast most cancers danger between these handled with GLP-1 receptor agonists and people handled with insulin (Wang et al., 2024). Data stay inadequate to totally assess long-term most cancers danger. Tirzepatide (Zepbound), a twin glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 RA, was FDA-approved in November 2023 for persistent weight administration (U.S. Food and Drug Administration, 2023). GIP is an incretin hormone that stimulates insulin secretion in a glucose-dependent method and will improve the metabolic results of GLP-1 when mixed in twin agonist therapies. In the SURMOUNT trials, tirzepatide produced a 15% to 22% complete physique weight discount over 72 weeks (Jastreboff et al., 2022). Like GLP-1 receptor agonists, tirzepatide's uncomfortable side effects are predominantly gastrointestinal, with nausea, vomiting, diarrhea, constipation, and stomach discomfort generally reported, affecting as much as 70% of sufferers, particularly throughout dose escalation (Jastreboff et al., 2022). Tirzepatide has demonstrated larger weight-loss efficacy and a extra favorable gastrointestinal side-effect profile in contrast with earlier GLP-1 receptor agonists in scientific trials. It has no recognized interplay with tamoxifen. Its long-term security in hormone-sensitive cancers stays unknown. Phentermine-topiramate (Qsymia) is a mixture drug used for persistent weight administration. Phentermine, a sympathomimetic amine, suppresses urge for food by growing the discharge of norepinephrine within the hypothalamus, whereas topiramate, an anticonvulsant, promotes weight reduction by enhancing satiety and growing vitality expenditure (Gadde et al., 2011). In scientific trials, this mix has resulted in common weight lack of 8% to 10% of complete physique weight over 56 weeks (Gadde et al., 2011). Phentermine is metabolized via the CYP3A4 pathway, much like tamoxifen. While there isn't any recognized interplay between the 2 drugs, this shared pathway might warrant warning. Reported uncomfortable side effects embody dry mouth, constipation, insomnia, paresthesia, and dysgeusia (Gadde et al., 2011). Potential severe opposed results embody elevated coronary heart price, elevated blood stress, cognitive impairment, and kidney stones (Gadde et al., 2011). Topiramate has been related to neuropsychiatric uncomfortable side effects, together with temper disturbances, nervousness, and cognitive slowing (Gadde et al., 2011). Bupropion, an antidepressant, and naltrexone, an opioid receptor antagonist, are mixed in a single medicine, Contrave, to cut back urge for food and meals cravings by modulating the mind's reward and stress pathways (Apovian et al., 2015). This mixture is believed to advertise weight reduction by lowering hedonic consuming and bettering emotional regulation, which can be significantly useful in managing the psychological points of weight achieve akin to melancholy and emotional consuming (Apovian et al., 2015). Clinical trials report common weight lack of 5% to 7% of baseline physique weight over 56 weeks (Apovian et al., 2015). Side results embody nausea, constipation, headache, dizziness, dry mouth, and insomnia. Naltrexone uncomfortable side effects embody nausea or constipation (Apovian et al., 2015). Because this medicine can have an effect on temper and sleep, it ought to be used cautiously in sufferers with melancholy, fatigue, or sleep issues, together with these associated to tamoxifen. Orlistat, a gastrointestinal lipase inhibitor, reduces dietary fats absorption (Apovian et al., 2015). In scientific trials, common weight reduction with orlistat has been reported as roughly 3% to five% of baseline physique weight over 52 weeks (Apovian et al., 2015). Orlistat's commonest uncomfortable side effects are gastrointestinal, together with diarrhea and oily stools (Apovian et al., 2015). Orlistat can cut back the absorption of fat-soluble nutritional vitamins (A, D, E, Ok), and warning ought to be used for these in danger for bone loss (Apovian et al., 2015).CLINICAL PRACTICE IMPLICATIONS For ladies struggling to handle tamoxifen-associated weight achieve regardless of life-style interventions, adjunctive pharmacotherapy might warrant consideration as a part of a patient-centered care plan. Weight administration recommendation ought to acknowledge the physiological challenges of tamoxifen-related weight achieve to keep away from reinforcing blame or disgrace in survivorship care. In a spotlight group, findings emphasize the significance of clear, person-centered communication about weight and weight administration, as ladies expressed a want to be seen as people somewhat than being supplied generalized recommendation (Nyrop et al., 2021). This reinforces the necessity for tailor-made, respectful discussions in survivorship care, significantly when addressing tamoxifen-associated weight achieve. Lifestyle interventions stay the cornerstone of survivorship care for ladies receiving tamoxifen. The 2024 American Cancer Society Nutrition and Physical Activity Guidelines for Cancer Survivors advocate a weight loss plan wealthy in greens, fruits, complete grains, legumes (significantly soy), and fiber, whereas limiting saturated fat. Additionally, the ACS recommends partaking in 150 to 300 minutes of moderate-intensity cardio exercise per week, akin to brisk strolling, swimming, or biking, or 75 to 150 minutes of vigorous-intensity exercise (Rock et al., 2022). In addition, power coaching is beneficial at the least twice weekly to have interaction main muscle teams (Rock et al., 2022). Resistance-based train helps mitigate tamoxifen-associated muscle loss, protect bone density, and cut back the danger of sarcopenia (Rock et al., 2022). These actions enhance insulin sensitivity, which can assist counteract tamoxifen-related metabolic adjustments (Jones & Parker, 2022). Although life-style interventions stay foundational, real-world adherence might be restricted by tamoxifen-induced fatigue, emotional misery, and metabolic adjustments that complicate weight reduction efforts. For ladies unable to attain significant weight management via life-style intervention alone, adjunctive pharmacotherapy might warrant consideration as a part of individualized, patient-centered survivorship care. Advanced practitioners (APs) play a vital position in mitigating tamoxifen-associated weight achieve and supporting survivorship care. Routine screening for weight change ought to be built-in into follow-up visits, permitting clinicians to establish early traits and intervene proactively. Additionally, APs are well-positioned to normalize conversations about weight achieve, lowering stigma and serving to survivors perceive the metabolic results of endocrine remedy. When clinically acceptable, APs ought to consider and provoke anti-obesity drugs utilizing present tips to tailor therapy to particular person danger profiles. Because protection for anti-obesity GLP-1 therapies is inconsistent throughout payers and out-of-pocket prices can exceed $1,000 per thirty days, significantly for these insured by Medicaid or high-deductible plans, APs may also function advocates, navigating prior authorizations and interesting denials when mandatory (Williams et al., 2024). Finally, efficient administration requires collaboration throughout oncology, major care, endocrine/weight problems specialists, and vitamin, making a coordinated, supportive framework that strengthens survivorship outcomes and enhances high quality of life.CONCLUSION Tamoxifen-associated weight achieve is a multifactorial difficulty that impacts metabolic well being and high quality of life. Lifestyle modification stays central to care. Anti-obesity drugs might supply a further instrument for sufferers who meet guideline-based standards. While the ACS emphasizes life-style modification and the ASCO and OMA define BMI-based standards for pharmacotherapy, the variation in guideline specificity round pharmacotherapy for weight administration in most cancers survivors reveals a spot in survivorship care. Advanced practitioners play an vital position in supporting weight administration for breast most cancers survivors receiving tamoxifen. Careful consideration should be given to potential interactions, uncomfortable side effects, and particular person affected person wants. Including most cancers survivors in future pharmacotherapy research can be important to constructing evidence-based suggestions. Clinical choices relating to anti-obesity drugs might contain collaboration with major care suppliers, weight problems specialists, or endocrinologists.Footnotes Dr. Fore-Williams has served on the audio system bureau for Novo Nordisk. Dr. Distler has no conflicts of curiosity to reveal.References American Cancer Society. (2024). Nutrition and bodily exercise tips for most cancers survivors. [DOI] [PMC free article] [PubMed] American Cancer Society. (2026). Key Statistics for Breast Cancer. Apovian, C. M., Aronne, L. J., Bessesen, D. H., McDonnell, M. E., Murad, M. H., Pagotto, U., & Ryan, D. H. (2015). Pharmacological administration of weight problems: An endocrine society scientific follow guideline. 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