Obesity and breast cancer: a narrative review of prognostic mechanisms, therapeutic challenges, and the role of weight management

Introduction

Background

Currently, we are facing two escalating public health epidemics: breast cancer (BC) and obesity (1,2). BC remains the most diagnosed malignancy among women globally, with 2.3 million new cases and 670,000 deaths reported in 2022 (2). In parallel, the prevalence of obesity has reached unprecedented levels; in 2022, one in eight people worldwide lived with obesity, a figure that has more than doubled since 1990 (1). This convergence is not coincidental. A vast and growing body of evidence has firmly established obesity not only as a concurrent condition but also as a critical, modifiable factor that profoundly influences BC biology, from initial risk to long-term prognosis and therapeutic response (3-6).

For decades, the clinical focus has been on the association between obesity and postmenopausal hormone receptor-positive (HR⁺) BC (6,7). However, this paradigm is shifting. It is now understood that excess adiposity is associated with a 35% to 40% increased risk of disease recurrence and mortality across multiple BC subtypes (6,7). This adverse impact depends on a complex network of biological mechanisms: obesity fosters a systemic and local state of chronic low-grade inflammation, metabolic dysregulation characterized by insulin resistance and hyperinsulinemia, and profound endocrine disruption. This milieu creates a microenvironment that is highly conducive to tumor initiation, progression, and metastasis (6,8,9).

Rationale and knowledge gap

The influence of obesity extends deep into the clinic, where it presents formidable challenges for effective treatment. It complicates surgical outcomes, alters the pharmacokinetics and toxicity of chemotherapy, drives resistance to endocrine therapy, and may modulate the response to novel targeted agents and immunotherapies (10). Further complicating the narrative is the “obesity paradox”, a counterintuitive observation from some studies suggesting a survival advantage for overweight or obese patients with cancer. This phenomenon has sparked intense debate, demanding rigorous scrutiny of both the biological plausibility and the methodological artifacts inherent in observational research (4,11-13).

Prior reviews have addressed the complex relationship between obesity and BC, highlighting subtype-specific prognostic patterns, biological mechanisms, and metabolic alterations (6,14,15). However, none have provided an integrated synthesis connecting updated prognostic evidence with recent advances in our understanding of metabolic and inflammatory pathways in obesity-related BC. This gap underscores the need for an updated narrative that bridges prognostic, biological, and interventional perspectives.

In response to these challenges, a new field of interventional research has emerged, focusing on mitigating the negative impact of obesity through weight management. While lifestyle interventions involving diet and exercise have demonstrated the ability to induce modest weight loss and improve metabolic biomarkers, their ability to definitively improve oncologic outcomes, such as survival, remains uncertain (16). The recent advent of highly effective pharmacological agents, such as glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), represents a potential paradigm shift, offering a level of weight reduction previously achievable only through bariatric surgery and opening new avenues for research (17,18). This review summarizes all the available emerging data on the use of these new medications in overweight/obese BC patients.

Objective

This narrative review aims to provide an expert-level synthesis of the current state of knowledge on the relationship between obesity and BC. This report dissects the prognostic landscape, elucidates the underlying biological drivers, deconstructs the obesity paradox, evaluates the impact of obesity on cancer therapy, and critically assesses the evolution of weight management interventions. The goal is to identify critical knowledge gaps and provide a framework to guide future research and clinical practice to improve outcomes for the growing population of patients with BC and obesity. We present this article in accordance with the Narrative Review reporting checklist (available at https://abs.amegroups.com/article/view/10.21037/abs-25-39/rc).

Methods

This narrative review synthesizes and critically evaluates the current body of evidence regarding the multifaceted relationship between obesity and BC.

We performed non-systematic literature searches to search for scientific peer-reviewed articles on specific subtopics, such as prognostic implications, treatment-related toxicity, biological mechanisms (e.g., inflammation, insulin resistance), and interventional strategies, including lifestyle modifications and pharmacological agents such as GLP-1 RAs. The primary PubMed search was conducted on February 1, 2025, and an updated search was performed on July 10, 2025 to capture newly published studies. The search focused primarily on publications from the last 10 years (January 2015 to July 2025) to ensure the inclusion of current evidence. The timeframe (January 2015 to July 2025) represents the period of eligible literature, whereas the dates of search execution refer to the specific days on which the database searches were performed. We prioritized high-impact evidence, including systematic reviews, meta-analyses, randomized controlled trials (RCTs), and large-scale prospective cohort studies, to develop a robust and evidence-based narrative. Since there was little peer-reviewed evidence on the use of the new GLP-1 RAs in BC, we also included recent meeting abstracts on this topic. Since this was a narrative review, we conducted the screening together, and consensus was reached meanwhile we wrote the review.

The search strategy employed for PubMed used a combination of medical subject headings (MeSH) and free-text terms: (“breast neoplasms” [MeSH] OR “breast cancer”) AND (“obesity” [MeSH] OR “body mass index” OR “overweight”) AND (“prognosis” [MeSH] OR “survival rate” OR “disease-free survival” OR “mortality”) Filters: English, Humans, last 10 years. For GLP-1 RAs. In addition to PubMed, complementary searches were performed in Google Scholar using and through manual review of abstracts from American Society of Clinical Oncology (ASCO) and American Association for Cancer Research (AACR) congresses [2024–2025] (Table 1).

Results: the multifaceted influence of obesity on BC

The prognostic landscape: a tale of subtypes and status

The overwhelming consensus from decades of research is that obesity is a significant negative prognostic factor in BC (3,5,7,8,19,20). A landmark meta-analysis demonstrated that women with early-stage BC and obesity at diagnosis face a 33% increased risk of BC-related mortality compared to their nonobese counterparts (21). This finding is consistently echoed in the literature, with multiple sources establishing a 35–40% greater risk of both disease recurrence and death associated with obesity (6). However, a deeper analysis reveals that the prognostic impact of obesity is not monolithic; rather, it is a highly context-dependent variable intricately modulated by the patient’s menopausal status and the tumor’s specific molecular subtype (7,22).

The association between obesity and poor prognosis is most robustly and consistently documented in postmenopausal women with HR⁺ BC (7,20,23). Studies have repeatedly shown that obesity in this population is associated with worse disease-free survival (DFS) and overall survival (OS). For instance, a 2023 study by Lammers et al. found that obesity was associated with a hazard ratio of 1.26 for worse DFS and a hazard ratio of 1.62 for worse OS in women aged ≤60 years with HR⁺ disease (23). This strong link has historically been attributed to increased peripheral production of estrogen in the adipose tissue of postmenopausal women, which could stimulate the growth of HR⁺ tumors (5,10).

For many years, the evidence linking obesity to outcomes in triple-negative BC (TNBC) and human epidermal growth factor receptor 2-positive (HER2⁺) BC has been inconsistent. However, more recent and larger studies have clarified this relationship, demonstrating that the detrimental effects of obesity are not restricted to HR⁺ disease. A pivotal 2015 study by Widschwendter et al. from the SUCCESS A trial revealed that severe obesity [body mass index (BMI) ≥35 kg/m²] was associated with significantly worse DFS and OS across all major subtypes, with particularly high hazard ratios in TNBC (hazard ratio =3.02) and HER2⁺ (hazard ratio =3.28) cancers (24). This finding strongly suggests that while estrogen-dependent pathways are a major driver of poor outcomes in HR⁺ obese women, other non-estrogenic mechanisms related to obesity, such as systemic inflammation and metabolic dysregulation, may contribute to worsening prognosis, even in the most aggressive, non-hormone-driven tumor types.

This more unified view coincides with the latest data from the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), presented in 2024. Analyzing over 206,000 women from 147 randomized trials, the EBCTCG confirmed a continuous, log-linear relationship between BMI and the risk of distant recurrence, with a rate ratio of 1.06 for every 5 kg/m² increase in BMI (25). This association was consistent regardless of adjuvant therapy, tumor characteristics, or estrogen receptor (ER) status. The EBCTCG data also refined the understanding of its interaction with menopausal status. While obesity is a poor prognostic factor in both groups, the absolute increase in 10-year distant recurrence risk appears more pronounced in premenopausal women (a 4% increase for node-positive patients) compared to postmenopausal women (a 2% increase). Therefore, obesity is a risk factor whose importance seems to vary by menopausal status, ER expression, and molecular BC subtype.

Biological mechanisms: the pro-tumorigenic microenvironment

Obesity adversely impacts prognosis by transforming adipose tissue from a passive energy reservoir into an active supporter of a pro-tumorigenic microenvironment. This shift is fueled by a self-perpetuating cycle of chronic inflammation and metabolic dysregulation, which are intrinsically linked and mutually reinforcing phenomena (8,9,26).

Chronic, low-grade inflammation is central to obesity’s impact on BC. In individuals with obesity, dying hypertrophic adipocytes attract immune cells, especially macrophages. These macrophages cluster around the necrotic fat cells, forming “crown-like structures” (CLS) in breast adipose tissue. These CLS produce pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), along with inflammatory mediators like prostaglandin E2 (PGE2). This localized inflammation then contributes to a systemic inflammatory state (27).

Obesity creates an inflammatory environment that disrupts metabolic and endocrine systems, significantly contributing to BC development. Cytokines like TNF-α, released from CLS, impair insulin signaling, leading to insulin resistance and hyperinsulinemia. Elevated insulin and insulin-like growth factor-1 (IGF-1) act as powerful mitogens, directly promoting cancer cell growth and survival through the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) pathway. This inflammatory state further fuels tumor growth. Inflammatory mediators such as PGE2, produced by the cyclooxygenase-2 (COX-2) enzyme, significantly increase aromatase expression in breast adipose stromal cells. This boosts the local conversion of androgens to estrogens, providing ample stimulation for HR⁺ tumors, which helps to explain the strong correlation between obesity and this specific BC subtype (28).

Finally, this dysfunctional state produces an imbalance of adipokines—hormones secreted by fat cells. Obesity leads to a marked increase in circulating leptin, a hormone that promotes cancer cell proliferation, angiogenesis, and migration. Simultaneously, it causes a sharp decrease in adiponectin, a beneficial adipokine that normally exerts anti-inflammatory and anti-proliferative effects. This altered leptin-to-adiponectin ratio further tilts the biological balance in favor of tumor growth and progression (28).

The interconnectedness of these pathways explains why obesity’s negative impact transcends HR-status; the inflammatory and insulin-driven components may expand obesity adverse prognostic implications to other BC subtypes that do not depend on ER signaling. Furthermore, these data allow us to advance the concept that it is not adiposity per se, but rather inflamed, metabolically dysfunctional adipose tissue that drives poor outcomes (27,28).

In summary, obesity fosters an inflammatory and metabolically dysregulated microenvironment that promotes tumor growth across BC subtypes. Table 2 summarizes these key biological pathways.

Deconstructing the “obesity paradox”

Contradicting the vast evidence of its detrimental effects, a subset of observational studies has reported a so-called “obesity paradox”, where patients with overweight or obesity demonstrate better survival outcomes (4,11-13). Such findings have been noted in specific clinical contexts, for instance, in patients with metastatic TNBC (13) or those receiving treatment with mTOR inhibitors like everolimus (29). While biologically intriguing, a rigorous methodological appraisal reveals that this paradox is likely not a true protective effect of adiposity but rather an epidemiological artifact due to inherent limitations in study design and the crude nature of BMI as a clinical metric (30).

Several key biases contribute to these findings:

• Reverse causation (30): this is an important confounder in oncology research. Aggressive, undiagnosed cancer often induces unintentional weight loss and muscle wasting (cachexia) before diagnosis. Consequently, a patient who was previously obese may be classified as “normal weight” at the time of study enrollment. This process artificially populates the normal-weight group with individuals who have more advanced disease and a poorer prognosis, while the obese group appears healthier in comparison. This may skew survival data, creating the illusion that obesity is protective.
• Collider stratification bias: this subtle but powerful bias arises when a study population is restricted to individuals who share a common outcome—in this case, a diagnosis of BC. Cancer is the “collider”. If two independent factors, such as obesity and smoking, both increase the risk of developing cancer, analyzing only cancer patients can create a distorted, inverse association between them. For example, among cancer patients, a non-obese individual may be more likely to be a heavy smoker (another potent cause of mortality) than an obese individual. When survival is analyzed, the higher mortality in the non-obese group (driven by smoking) can make obesity appear protective by comparison (30).
• Residual confounding: observational studies often struggle to fully account for all potential confounding variables. Factors like detailed smoking history, physical activity levels, diet quality, and socioeconomic status are difficult to measure precisely and can remain as residual confounders that can distort the true relationship between BMI and survival (30).

Beyond these biases, the most fundamental methodological flaw in studies reporting an obesity paradox is their reliance on BMI. BMI is a simple measure of mass relative to height and cannot distinguish between metabolically active muscle tissue and adipose tissue, nor does it describe fat distribution (e.g., visceral vs. subcutaneous) (30,31). This is critical in cancer patients, who frequently experience changes in body composition. A high BMI can mask the presence of sarcopenia (low muscle mass), a condition strongly and independently associated with higher treatment toxicity, surgical complications, and worse survival (32). Conversely, a “normal” BMI can hide excess visceral adiposity, another key driver of poor outcomes. When studies move beyond BMI and use more precise techniques like computed tomography (CT) to quantify body composition, the paradox often vanishes. For instance, a 2018 paper by Caan et al. (33) showed that while BMI alone was not a significant predictor of mortality, high adiposity and low muscle mass (sarcopenia) were strongly associated with worse survival. This evidence strongly suggests that the “obesity paradox” is more accurately a “BMI paradox” (33). Future research must prioritize direct assessments of body composition to generate clinically meaningful data.

The only area in which an obesity paradox may indeed exist in BC is immunotherapy as will be discussed below (34).

Obesity as a modulator of cancer therapy

Obesity does not merely coexist with BC; it actively interferes with the delivery, efficacy, and toxicity of nearly every therapeutic modality, creating a distinct and more challenging clinical landscape (10,35).

Surgery and radiotherapy: the physical burden of excess adipose tissue complicates procedural interventions. Patients with obesity experience higher rates of anesthesia-related challenges, postoperative complications such as surgical site infections and bleeding, and a significantly increased risk of developing chronic lymphedema following axillary surgery. Furthermore, sentinel lymph node mapping, a crucial staging procedure, has a higher failure rate in obese individuals. For those undergoing breast-conserving therapy, obesity is associated with poorer cosmetic outcomes and potentially higher rates of local recurrence after radiation (10,35).

Chemotherapy: the impact on chemotherapy is multifaceted. For years, concerns about toxicity led to routine “dose capping”, in which chemotherapy for obese patients was reduced or based on ideal instead of actual body weight. This practice is now known to cause systematic underdosing, compromising treatment efficacy and leading to worse survival outcomes (10,35). Obesity can affect drug pharmacology, even with weight-based dosing. The efficacy of lipophilic drugs like docetaxel may be reduced, possibly due to sequestration in the larger volume of adipose tissue, which prevents the drug from reaching the tumor at therapeutic concentrations (36).

Endocrine therapy: in postmenopausal women, the efficacy of aromatase inhibitors (AIs) can decrease by obesity. The increased volume of adipose tissue and upregulated aromatase activity result in higher baseline estrogen levels that are insufficiently suppressed by standard AI doses, potentially creating an escape route for HR⁺ tumors (10). Beyond this, the metabolic milieu of obesity—characterized by hyperinsulinemia and inflammation—can activate alternative signaling pathways like PI3K/Akt, a well-established mechanism of endocrine resistance (26).

Targeted and novel therapies: the influence of obesity on newer agents is an area of active and complex investigation.

• CDK4/6 inhibitors: evidence for this class is conflicting. A sub-analysis of the PALLAS trial found no impact of BMI on the efficacy of palbociclib. However, other real-world studies have hinted at a potential “paradox”, with overweight patients showing a trend toward better progression-free survival (PFS) compared to normal-weight or obese patients (37). In terms of toxicity, similar to chemotherapy, obese patients often experience less frequent and severe neutropenia (38). These inconsistent findings suggest that BMI is an inadequate proxy, and that outcomes may be more closely related to specific body composition parameters like visceral adipose tissue, which one meta-analysis found was associated with significant PFS gains (39).
• Immunotherapy: this is the one area where a biologically plausible obesity paradox may exist (34,40). The state of chronic, low-grade inflammation and metabolic stress in obesity can lead to T-cell exhaustion, characterized by increased expression of immune checkpoint proteins like PD-1 and its ligand, PD-L1. This pre-existing immune suppression may render tumors in obese patients “pre-primed” and more susceptible to the effects of immune checkpoint inhibitors (ICIs) (40). Preliminary data in TNBC suggest that obese patients may have higher rates of pathologic complete response to neoadjuvant immunotherapy (34). This turns a major risk factor into a potential predictive biomarker, representing a complete change in thinking in how the field views the interaction between host metabolism and anti-tumor immunity.

In summary, obesity interferes with the safety and effectiveness of multiple BC treatments, influencing outcomes across modalities. Table 3 provides a concise overview of these therapy-specific effects.

Interventional strategies: the pursuit of improved outcomes

Given the profound negative impact of obesity on BC prognosis, a critical area of research has focused on whether this risk is modifiable through weight management interventions. This field is at a major inflection point, moving from an era dominated by lifestyle interventions to a new frontier of potent pharmacological agents.

Lifestyle interventions (diet and exercise): for over two decades, RCTs have tested the impact of lifestyle interventions on BC outcomes. Landmark studies like the Women’s Intervention Nutrition Study (WINS) (41) and SUCCESS trial (42,43) provided valuable insights. These trials, along with numerous smaller studies, have consistently shown that structured programs involving dietary changes (e.g., low-fat, plant-based diets) and increased physical activity can successfully induce modest but clinically meaningful weight loss, typically in the range of 2% to 6% of baseline body weight (44). These interventions have also been shown to favorably modulate key biological mediators, reducing estradiol levels (45), improving markers of glucose homeostasis, and reducing levels of inflammatory cytokines (8).

It is clear that weight loss interventions, combining diet, exercise, and behavior modification, can significantly reduce the weight of BC patients (16). However, the efficacy of these weight-loss interventions on oncological outcomes such as DFS and OS after a BC diagnosis remains inconclusive due to the limited number, small sample sizes, and short follow-up duration of many interventional studies according to a meta-analysis by Playdon et al. (16). Possibly the small weight loss produced by these non-pharmacologic interventions may help to explain why these studies do not lead in aggregate to statistically significant changes in DFS or OS (16).

The new frontier: pharmacological intervention with GLP-1 RAs: given the limited effectiveness of lifestyle interventions, there’s growing interest in powerful pharmacological solutions. These could offer a less invasive alternative to bariatric surgery, currently the most effective weight-loss treatment, thereby addressing a significant therapeutic gap (46,47). GLP-1 RAs, such as semaglutide and tirzepatide, represent a major change in the field. In the general population, these agents induce substantial weight loss of 15% to 22%, a magnitude previously only achievable with bariatric surgery (48).

Early, retrospective data on their use in BC survivors are now emerging. These studies confirm that GLP-1 RAs are effective (18,49), but its weight loss effect appears to be attenuated in this population, with average reductions closer to 3–5% (17). This blunted response is particularly notable in patients concurrently receiving endocrine therapy, suggesting a possible drug-drug interaction or an alteration in metabolic physiology unique to this patient group (17).

Regarding oncologic safety and efficacy, the current real-world evidence is preliminary but reassuring. Retrospective analyses have not found an increased risk of BC recurrence in patients using GLP-1 RAs (17,18,49). Intriguingly, one large study reported a significant improvement in all-cause mortality, though not in DFS, suggesting that the primary benefit may stem from cardiovascular protection in this high-risk population (50).

TRIM-EBC trial (51) illustrates the new directions clinical trials may pursue in this area. This innovative study will test whether potent weight loss induced by tirzepatide in high-risk, early-stage BC patients can lead to the clearance of circulating tumor DNA (ctDNA)—a sensitive marker of minimal residual disease and a strong predictor of recurrence. By using ctDNA as a primary endpoint, TRIM-EBC can provide a much faster assessment of the direct impact of pharmacological weight loss on cancer biology. This trial, if positive, could establish metabolic management as a central pillar of BC treatment.

In summary, weight-management strategies range from modest lifestyle programs to emerging pharmacologic approaches, each with distinct effects on outcomes. Table 4 provides a comparative summary of major weight management trials in BC.

Discussion

The evidence synthesized in this review suggests that the relationship between obesity and BC is complex and clinically significant. It is no longer sufficient to view obesity as a simple comorbidity. Instead, it must be recognized as a fundamental modulator of tumor biology that influences prognosis and directly interferes with the efficacy and toxicity of treatment (6,10). The overarching theme is that the negative impact of obesity is driven by a network of interconnected inflammatory, metabolic, and hormonal pathways (26,27). This biological reality transcends simple metrics like BMI, demanding a more nuanced clinical approach (31).

The “obesity paradox” is now seen as a potentially settled methodological issue (31). The consistent demonstration of biases such as reverse causation, collider stratification, and the profound inadequacy of BMI as a proxy for metabolic health indicates that the paradoxical survival benefit seen in some studies is an artifact, not a biological reality. This conclusion has a critical implication: the field must move beyond BMI and toward a new standard that incorporates more precise measures of body composition, such as visceral adiposity and muscle mass (sarcopenia), to accurately risk-stratify patients and understand treatment effects (31).

These advances also apply to patient counseling about metabolic demands in cancer. While cancer cells demonstrate a high reliance on glucose via the Warburg effect, contributing to the rationale for limiting excessive carbohydrate intake, current supportive care often emphasizes high-carbohydrate diets primarily to combat weight loss and cachexia during intensive treatment. The evidence underscores the necessity of individualized dietary counseling, incorporating potential benefits from controlled fasting or low-carbohydrate regimens alongside careful management of nutritional status. This dual approach can empower patients to make informed lifestyle choices that balance metabolic targeting and overall health during cancer therapy, supporting integration of metabolic management into oncologic care (1,2). The clinical implications of the findings here described are substantial. The fact that obesity alters the therapeutic window for chemotherapy and drives resistance to endocrine therapy necessitates the integration of metabolic assessment and nutritional counseling into the standard of care for all BC patients (10).

Non-systematic, narrative reviews are prone to article selection bias but allow for a wider coverage of a particular field that allowed us to map out critical knowledge gaps that still remain in this area, pointing toward clear directions for future research, such as:

• Prospective pharmacological intervention trials: the most urgent need is for large-scale, prospective, randomized trials to definitively establish the oncologic safety and efficacy of GLP-1 RAs. While the TRIM-EBC trial and its ctDNA endpoint represent a crucial first step, studies with long-term follow-up for hard clinical endpoints like DFS and OS are essential to confirm a survival benefit and justify their widespread use in the oncology setting.
• Mechanistic understanding of GLP-1 RA effects: elucidating the mechanisms behind the attenuated weight loss effect of GLP-1 RAs observed in BC survivors is a priority. Investigating potential pharmacokinetic interactions with endocrine therapies and exploring whether the underlying cancer biology alters metabolic responses to these agents, and if there are adherence issues in this population of patients, are key priorities.
• A practical, tiered approach can improve cancer risk assessment beyond BMI alone: all patients should have BMI and waist circumference measured, those at higher risk should be evaluated with metabolic blood biomarkers, and, when available, muscle and visceral fat can be quantified via CT scans. The visceral adiposity index (VAI)—which incorporates waist circumference, BMI, triglycerides, and high-density lipoprotein cholesterol—serves as a validated, non-invasive marker of visceral adiposity and metabolic dysfunction, independently linked to cancer risk and readily incorporated into clinical practice. Future research should focus on biomarker-guided interventions, using predictive markers such as CRP, adipokines, and the VAI to personalize weight management: for example, a patient with elevated inflammatory markers and significant visceral adiposity may benefit from aggressive intervention, while another patient with similar BMI but better metabolic health may not. Combining inflammatory, metabolic, and body composition markers could enable the creation of a practical “metabolic risk score”, thereby tailoring interventions to those most likely to benefit. This framework makes personalized risk assessment and early intervention feasible and actionable in standard oncology care.

Conclusions

Current evidence indicates that obesity management should be a primary focus in comprehensive BC care together with other therapeutic modalities such as surgery, radiation, and systemic chemotherapy. While lifestyle interventions have laid an important foundation, they have proven insufficient to consistently reverse the adverse oncologic outcomes associated with excess adiposity. The advent of potent pharmacological agents like GLP-1 RAs marks a pivotal moment, offering an unprecedented opportunity to modify this critical risk factor. However, their role in improving cancer-specific outcomes remains to be proven. Future research must prioritize well-designed prospective trials to confirm the oncologic benefit of these agents and to develop biomarker-driven strategies that personalize metabolic interventions. By addressing the host and the tumor, the field has the potential to significantly improve survival and quality of life for the growing number of women facing the dual burden of BC and obesity.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://abs.amegroups.com/article/view/10.21037/abs-25-39/rc

Peer Review File: Available at https://abs.amegroups.com/article/view/10.21037/abs-25-39/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://abs.amegroups.com/article/view/10.21037/abs-25-39/coif). A.d.G. serves as an unpaid editorial board member of Annals of Breast Surgery from May 2025 to December 2026. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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