Although clinicians widely recognize obesity as a modifiable risk factor, achieving and sustaining meaningful weight loss remains a complex challenge in the clinical setting. For decades, the oncology community has acknowledged the epidemiological links between elevated body mass index (BMI) and poor oncologic outcomes. However, translating that knowledge into actionable, effective, and sustainable clinical interventions has proven remarkably difficult. Patients frequently navigate a gauntlet of treatments, ranging from chemotherapy to multi-year endocrine regimens, that disrupt metabolic homeostasis, alter body composition, and actively promote weight gain.
Emerging data suggest that metabolic health is not just a secondary quality-of-life concern but a primary driver of long-term survival. This is particularly evident in breast cancer, where high cure rates mean that cardiovascular disease, rather than cancer recurrence, has become the leading cause of death following a diagnosis. With the explosive rise of glucagon-like peptide-1 (GLP-1) receptor agonists in general medicine, the oncologic community is evaluating how these pharmacologic tools, alongside structured exercise and digital lifestyle interventions, can be integrated into standard oncologic care.
To explore the clinical realities, data gaps, and future directions of metabolic management, CancerNetwork® spoke with Jennifer Ligibel, MD, professor at Harvard Medical School and a senior physician in the Breast Oncology Center at the Dana-Farber Cancer Institute, and Sherry Shen, MD, assistant attending physician at Memorial Sloan Kettering Cancer Center (MSKCC). Separately, the pair discussed a rapidly shifting paradigm: one where weight management is moving from an afterthought in survivorship to an active clinical mandate.
How Obesity Impacts Cancer Risk
The biological mechanisms connecting excess adiposity to malignant disease are diverse and profound. Obesity induces a state of chronic, low-grade systemic inflammation, elevates circulating levels of insulin and insulin-like growth factors, and alters adipokine profiles, all of which create a permissive environment for tumor development, progression, and metastasis.1
“There are hundreds of studies that show us that obesity, in particular, is linked to a higher risk of developing 13 different cancers and a higher risk of recurrence and mortality in some of our most common cancers: breast cancer, colon cancer, and gynecologic cancers,” Ligibel said.2 “We honestly don’t have a clear answer of knowing exactly how much weight somebody needs to lose to either prevent them from developing cancer or to improve their outcomes once cancer is already developed.”
According to Ligibel, the most compelling data demonstrating that weight loss can alter the trajectory of cancer risk have come from the bariatric surgery literature. Large-scale, matched cohort studies, like the one conducted by Schauer et al., have consistently shown that individuals who undergo bariatric surgery experience a dramatically lower risk of developing obesity-related malignancies compared with historical controls matched by age, weight, gender, and comorbidities.3
However, bariatric surgery results in weight loss of 25% to 35% of total body weight within 1 to 2 years of surgery.4 It remains unclear whether such extreme weight loss is mandatory to achieve an oncologic benefit, according to Ligibel, or if more moderate reductions are sufficient.
This uncertainty is precisely why the oncology community is viewing the rise of GLP-1 receptor agonists with profound interest. These medications achieve substantial weight loss that bridges the gap between traditional lifestyle modifications and surgical interventions, offering an unprecedented opportunity to evaluate the impact of non-surgical weight reduction on cancer incidence and recurrence.
GLP-1 Use in the Breast Cancer Space
The intersection of weight management and oncology is particularly critical within the breast cancer space, where standard-of-care treatments systematically undermine a patient’s metabolic health. Shen noted that the trajectory of post-diagnosis weight gain may begin during active chemotherapy, which is driven by high-volume intravenous fluids, mandatory antiemetic corticosteroids, disrupted dietary patterns, and sudden drops in physical activity. This short-term metabolic shock occurs over months, and it is frequently followed by long-term endocrine therapies that suppress or block estrogen for 5 to 10 years.
Furthermore, many patients with breast cancer are naturally perimenopausal or postmenopausal at diagnosis, or they experience treatment-induced menopause secondary to gonadotropin-releasing hormone (GnRH) agonists or chemotherapy-induced ovarian failure. Shen highlighted that these factors could play a role in weight gain after diagnosis. She went on to cite that those who have weight gain of over 10% of the diagnosis body weight may experience worse long-term outcomes.
While weight gain is a primary concern, maintaining cardiovascular health, including cardiometabolic health, is significant as well. Shen cited that one of the leading causes of death for patients with breast cancer is cardiovascular disease.5
The Clinical Utility of GLP-1 Agonists
To address this clear unmet need, researchers have begun evaluating the real-world efficacy of GLP-1 receptor agonists in cancer survivors and those undergoing treatment. Shen and her colleagues at MSKCC recently published a retrospective cohort study in the journal ONCOLOGY, evaluating 75 patients across various stages and receptor statuses of breast cancer who were prescribed GLP-1 agonists.6 The study, which was among the very first published on this topic, demonstrated a mean weight loss of approximately 5% at 12 months.
While a 5% reduction is clinically meaningful, it is notably lower than the weight loss observed in the general population. Shen acknowledged that this was a small population, perhaps one of the first assessing GLP-1 use in breast cancer. When she compared them with other phase 3 clinical trials for weight management in non-cancer populations, GLP-1 agonists demonstrated an average weight loss ranging from 8% up to nearly 20% with highly potent dual-incretin agents like tirzepatide (Zepbound).
In the study, approximately 80% of the patients in the MSKCC cohort were receiving a GLP-1 agonist for a primary type 2 diabetes indication rather than dedicated weight management, meaning they underwent different dosing schedules. However, a subsequent, larger study out of MD Anderson Cancer Center led by Jasmine Sukumar, MD, confirmed this trend, demonstrating a modest average weight loss in the 2% to 3% range with a similarly high proportion of patients on diabetes-specific dosing.
“One of the real takeaways here is that it’s possible that patients with breast cancer, especially those who are taking active anti-cancer treatments, may have a harder time losing weight, even with GLP-1s. On the other hand, 5% is a meaningful amount of weight loss,” Shen said.
Despite this modest response, a 5% reduction remains a vital therapeutic tool. Because a 10% weight gain drives poor outcomes, a 5% weight loss, when combined with proactive lifestyle modifications, can effectively blunt or reverse that dangerous upward trajectory, profoundly improving a patient’s body image, quality of life, and clinical adherence to multi-year endocrine regimens.
Whether GLP-1 receptor agonists directly reduce the risk of breast cancer recurrence remains an unanswered question. However, Shen highlighted that there is a signal towards improved overall survival because of the benefit toward improved control of A1c and glucose. Additionally, no study to date has shown an increased risk of cancer recurrence or progression in patients utilizing these medications, providing clinicians with the reassurance needed to consider these drugs for patients struggling with severe metabolic dysfunction.
Timing and Safety Considerations for GLP-1 Use
As enthusiasm for GLP-1 agonists grows, oncologists must consider the safety associated with these interventions. Emerging consensus and draft guidelines from the European Society for Medical Oncology (ESMO) suggest a nuanced approach, strongly advocating for caution and advising against the initiation of GLP-1 agonists during active intensive chemotherapy or immunotherapy.7
“There were a few small retrospective studies that suggested both in the triple-negative space and in the HER2-positive space that when GLP-1s were given alongside neoadjuvant treatment, that rates of pathologic complete response may be lower. That’s concerning,” Shen said.
The exact mechanism behind this finding remains unproven, as the studies are still in abstract form, so knowing the reasoning behind this is still difficult. Shen wondered if there was an independent effect associated with GLP-1 use; perhaps the adverse effects of nausea or vomiting did not allow the patient to tolerate as much chemotherapy.
Shen and her team will wait to utilize GLP-1s in the long-term once chemotherapy is completed. Shen applies a similar principle to targeted oral therapies, such as the CDK4/6 inhibitor abemaciclib (Verzenio), which is utilized in the adjuvant and metastatic hormone receptor–positive settings. Abemaciclib can be associated with significant gastrointestinal toxicity, primarily severe diarrhea and nausea.
“I tend to tell those patients to wait until the CDK4/6 inhibitors are done so that we don’t have these overlapping toxicities. Then, when you’re looking at several more years of endocrine therapy, that may be the right time to start the GLP-1,” Shen said.
The Role of Exercise and Digital Health
GLP-1s are designed to mimic active hormones to slow digestion, control blood sugar, and tell your brain when you’re full. Overall, this will help to control your appetite, cravings, and allow for longer satiety.8
However, this reduction can result in the body shedding not only adipose tissue but also vital lean skeletal muscle mass. For patients with cancer, this is something clinicians need to consider and monitor carefully.
Finding the perfect balance can be difficult. The effects of cancer treatment may leave patients with no appetite or feeling lethargic. This is where the utilization of exercise oncology should be integrated.
Ligibel highlighted that exercise possesses profound, proven therapeutic benefits that exist completely independently of weight management. Although physical activity is essential for keeping weight off over the long term, exercise oncology can alter outcomes.
For example, the CHALLENGE trial, with the cost analysis of the study presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, provided definitive prospective evidence of this benefit.9 Previous findings from the 2025 ASCO Annual Meeting showed that the trial randomly assigned patients with colorectal cancer who had completed all conventional curative therapies to either a highly structured, aerobic exercise program (primarily walking) or standard, passive healthy lifestyle advice.10
The results showed that patients in the structured exercise arm experienced a reduction in the risk of colorectal cancer recurrence, alongside a reduction in overall mortality. The data also showed a reduction in the incidence of entirely new primary malignancies, including new breast, colon, and prostate cancers. This landmark study provided definitive proof that physical activity is a life-saving oncologic intervention capable of altering tumor biology and preventing disease recurrence.
Despite these clear benefits, immense structural barriers prevent the seamless integration of exercise and weight management into standard oncologic practice. Chief among these is the complete lack of reimbursement infrastructure. Commercial insurance and public health programs routinely refuse to cover the costs of structured exercise oncology programs, physical therapists, or formal medical weight management for cancer survivors.
“That study gives us incredible insight into the value of exercise, all the way to prevention of recurrence and mortality. [There was] clear evidence that exercise is an important part of the way that we could think about preventing cancer and treating people with potentially curable disease,” Ligibel said.
Ligibel then highlighted that most cancer centers lack the infrastructure and dedicated staff required to deliver these programs. She said that this is something that shouldn’t fall solely on the patients. Financial toxicity with cancer care is prevalent; putting that on the patient after treatment isn’t feasible.
To bridge this operational gap, clinicians are increasingly turning to digital health technologies. Mobile health applications, wearable fitness trackers, and remote monitoring platforms represent highly scalable, cost-effective tools that can seamlessly integrate into a patient’s daily routine.
Shen and her team have reported on weight loss in breast cancer survivors, which was monitored through digital technology.11 The study found a 5% or more weight loss associated with the app use in tandem with articles read (P = 0.012), weights logged (P = 0.006), food records logged (P = 0.001), messages sent (P = 0.001), and application open count (P = 0.014). Additionally, a significant increase was observed in mean daily step count (P = 0.004), GPAQ scores (P = 0.002), and Body Image Scale scores (P < 0.001). Overall, the study showed that those who were highly engaged with the technology experienced clinically significant weight loss, increased physical activity, maintenance of an energy-restricted diet, and improvements in body image.
While these digital applications do not solve the time scarcity issue that many patients face, they do, however, provide a structured, accessible framework for behavioral modification.
“These modern tools are adapted to our current technology-filled life that can aid with kickstarting the weight loss journey and help educate our patients…something like an app that you can engage with over and over and learn from over time while seeing those small modifications that you’ve made in diet or physical activity track with changes in weight can be helpful. We’re busy. Trying to figure out a way to integrate all these things into our lives is tough but so important,” Shen said.
Ongoing Clinical Trials in the GLP-1 Space
To fully transition from real-world retrospective observations to robust, evidence-based standard care, prospective clinical trials are being launched. Several small, highly innovative prospective trials are currently underway across diverse clinical settings.
Shen noted that in the preventative space, a trial is investigating the utility of GLP-1 agonists in patients diagnosed with high-risk, non-invasive breast lesions. This study is tracking changes in mammographic breast density and monitoring the eventual development of invasive carcinoma to determine if systemic GLP-1 receptor activation has any influence. Within the adjuvant setting, prospective trials are actively accruing patients with breast cancer with an elevated BMI to take GLP-1 receptor agonists concurrently with standard endocrine therapy.
For Shen, these studies represent a vital step forward; they incorporate mandatory, serial collections of blood and tumor tissue, allowing researchers to evaluate at a microscopic and molecular level exactly how GLP-1 therapies modify circulating inflammatory cytokines, insulin signaling pathways, and the systemic metabolic microenvironment.
Looking Ahead to Integrating Exercise Oncology and GLP-1 Use in Cancer Care
The management of obesity and metabolic health within oncology has officially evolved past basic lifestyle advice. The clinical realities of treatment-induced menopause, profound metabolic deceleration, and the terrifying reality of cardiovascular mortality demand highly sophisticated, multidisciplinary interventions. The integration of GLP-1 receptor agonists into this space represents a major milestone, offering a potent pharmacologic tool to combat weight gain and profoundly improve systemic cardiometabolic health.
“There’s a lot we know, but there’s so much that we don’t know,” Ligibel said. “There are different things that happen when you have bariatric surgery and when you take a medication vs when you lose weight via diet and exercise. Does it make a difference? Is it about how much weight [is lost], or does how you do it make a difference, too? Those are important questions aside from [whether] this help cures cancer, which we don’t know yet, but we’re hopeful.”
However, as the data from major conferences like ASCO undoubtedly show, these medications are not a standalone cure. They must be paired with exercise oncology to preserve skeletal muscle and bone density and supported by modern digital health tools to drive permanent behavioral change.
“There’s just so much more that we’re still learning about these drugs. It’s very much an evolving field of what GLP-1s look like in those with a cancer diagnosis, so a lot more to come, and stay tuned,” Shen concluded.
References
- Divella R, De Luca R, Abbate I, Naglieri E, Daniele A. Obesity and cancer: the role of adipose tissue and adipo-cytokines-induced chronic inflammation. J Cancer. 2016;7(15):2346-2359. doi:10.7150/jca.16884
- Obesity and cancer. CDC. June 11, 2025. Accessed June 17, 2026. https://tinyurl.com/32mjn9wv
- Schauer DP, Feigelson HS, Koebnick C, et al. Bariatric surgery and the risk of cancer in a large multisite cohort. Ann Surg. 2019;269(1):95-101. doi:10.1097/SLA.0000000000002525
- Economopoulos KP. Why bariatric surgery is life-changing: what the research shows. Brown Health. January 22, 2026. Accessed June 17, 2026. https://tinyurl.com/5d2tezs2
- Contiero P, Boffi R, Borgini A, et al. Causes of death in women with breast cancer: a risks and rates study on a population-based cohort. Front Oncol. 2023;13:1270877. doi:10.3389/fonc.2023.1270877
- Shen S, Liu B, Fanti C, et al. GLP-1 receptor agonist use and weight change in patients with breast cancer. Oncology (Williston Park). 2025;null(7):294-296. doi:10.46883/2025.25921046
- Iyengar NM. GLP-1 receptor agonists and breast cancer: metabolic insights and clinical implications. Presented at: 43rd Miami Breast Cancer Conference; March 5-8, 2026.
- Can GLP-1s help reduce the risk of cancer? American Cancer Society. March 26, 2026. Accessed June 17, 2026. https://tinyurl.com/33brk8bk
- Chan KK, Chu RW, Cheung MC, et al. Structured exercise program following adjuvant chemotherapy for colon cancer: a cost-utility analysis of the CHALLENGE trial. J Clin Oncol. 2026;44(suppl 16):3507. doi:10.1200/JCO.2026.44.16_suppl.3507
- Courneya KS, Vardy JL, O’Callaghan CJ, et al. Structured exercise after adjuvant chemotherapy for colon cancer. N Engl J Med. 2025;393(1):13-25. doi:10.1056/NEJMoa2502760
- Shen S, Salehi E, White C, Chen Y, Iyengar NM. Evaluation of a mobile behavior change program for weight loss in breast cancer survivors. NPJ Breast Cancer. 2024;10(1):53. doi:10.1038/s41523-024-00659-x
