Posted on January 11, 2024

By Haleemah Atobiloye, M.A., she/hers, Program Manager  

Solving the Intricate Puzzle: Updates in the Obesity-Breast Cancer Connection

At last year’s San Antonio Breast Cancer Symposium (SABCS), I attended the Spotlight Discussion on Obesity and Breast Cancer session and shared my stance on the subject of obesity and breast cancer. At this year’s SABCS, I was interested in hearing what, if anything, had changed on this matter. My curiosity led me to explore any developments, prompting my attendance at the Overcoming Obesity-Associated Breast Cancer Risk panel session moderated by Abenaa Brewster MD, MHS.” 

 The first presentation of this panel was titled Breaking the Obesity-Breast Cancer Link: Comparing Diet, Drug, and Surgical Approaches, by Dr. Stephen D. Hursting from the University of North Carolina. The central question being explored by Dr. Hursting was how to disrupt the obesity-cancer connection, comparing the efficacy of diet, drugs, and bariatric surgery. To explore this question, the presentation highlighted findings gathered from several large-scale research reports, such as the American Institute for Cancer Research (AICR) World Cancer Research expert report and the International Agency for Research on Cancer (IARC) Cancer Prevention Handbook. The following are some of my takeaways from this presentation: 

  • The obesity-cancer link involves factors which include the insulin–IGF-1 axis, sex hormones, and adipokines, which are cytokines derived from adipocytes. These factors are closely tied to the endocrine and paracrine dysregulation of adipose tissue in individuals with obesity. This statement explains that there is a connection between obesity and cancer, and this connection is influenced by various factors. These factors include the insulin–IGF-1 axis (insulin-like growth factor 1), sex hormones, and adipokines. Adipokines are cytokines (proteins involved in cell signaling) that are produced by adipocytes, which are fat cells. The interplay of these factors is closely associated with the disruption of normal hormonal regulation within the endocrine (hormonal signaling throughout the body) and paracrine (local signaling between cells) systems in the adipose tissue of individuals who are obese. Essentially, the statement highlights the complex hormonal and cellular changes in the fat tissue of obese individuals that contribute to the link between obesity and an increased risk of cancer. 
  • In the studies examined, comparisons were made between different interventions, including calorie restriction, low-fat diets, and bariatric surgery. Findings from the data reveal that both bariatric surgery and diet-induced weight loss were effective at reversing pre-cancer effects, with calorie restriction showing a consistent advantage in various studies.  
  • It is also important to add that the presenter also mentioned that there is still limited evidence on whether weight loss can reverse the pre-cancer effects of chronic obesity. 
  • There’s a need for precision in interventions, considering the heterogeneity and diverse effects of obesity in different individuals. This statement explains that because everyone is not the same, precision in interventions for obesity and breast cancer is important. Obesity can affect people differently, and it might raise the risk of breast cancer in some but not in others. Precision means treating each person based on their unique characteristics, like their body, genes, and lifestyle. This personalized approach helps healthcare providers come up with strategies that work best for each individual, increasing the chances of preventing or treating breast cancer effectively. It’s like having a health plan that’s just for you, making it more likely to succeed based on what your body needs. 

Dr. Randy Seeley, from the University of Michigan, was the second presenter on this panel. Dr. Seeley’s presentation was titled Mechanisms for the Effects of Incretin and Dual-Incretin to Produce Substantial Weight Loss. The presentation revolved around body weight regulation, and the pivotal role of the brain in this process. Using himself as an example, Dr. Seeley illustrates that for an average male, the annual caloric intake and expenditure balance out at 900,000 calories, resulting in a stable body weight. He underscores the seemingly small impact of gaining just one pound annually, but stresses its cumulative nature over time.  

My key takeaway from this presentation is that, in the United States, the average yearly weight gain per person is approximately one pound. Dr. Seeley draws attention to the significance of this seemingly minor increase, equating it to a 4,000-calorie discrepancy between intake and expenditure. This translates to 11 calories a day, likened to the consumption of a single potato chip. He emphasizes that this daily calorie–intake difference plays a crucial role in determining whether a society leans towards obesity or maintains a lean profile—underscoring the importance of recognizing and addressing these marginal variations in caloric balance. 

In the third and final presentation, titled Impact of Exercise on Breast Cancer Outcomes, Dr. Kerry Courneya, from the University of Alberta adds their research findings to into solving the intricate puzzle of obesity-associated breast cancer risk. The presentation shifts the focus towards considering exercise as a breast cancer treatment. According to the presenter, this perspective marks a departure from the conventional approach in research, which primarily addresses exercise from a public health or cancer survivorship standpoint, often prescribing a single exercise regimen for all breast cancer survivors. This is a new field of research, and Dr. Courneya using the limited large-scale randomized controlled trials that pertaining to exercise and breast cancer outcomes, provides insights that show that exercise may improve the response of tumors to drugs, leading to better breast cancer treatment outcomes. 

The following are some of the preclinical studies the presenter used to illustrate the potential anti-cancer effects of exercise and to highlight the biological mechanisms through which exercise may influence tumor growth and spread: 

Number of Studies  

  • The presenter mentions that there are approximately 50 preclinical studies on exercise and tumor growth, and there are about 15 preclinical studies combining exercise with chemotherapy, immunotherapy, or radiation therapy. 

General Finding  

  • The general finding from these studies is that exercise tends to slow the growth and spread of tumors. 

Biological Mechanisms  

  • The biological mechanisms underlying the effects of exercise on tumors are discussed. These mechanisms include improvements in insulin, insulin-like growth factor (IGF), anti-inflammatory markers, effects on the immune system, and activation of apoptosis pathways. Exercise was also found to enhance drug response by improving angiogenesis and increasing blood perfusion into tumors. Angiogenesis is the creation of new blood vessels from existing ones, supporting normal processes like tissue growth. However, in cancer, tumors hijack this process to establish a blood supply, facilitating their growth and spread. Understanding and targeting angiogenesis is key in developing treatments for cancer and other diseases. 

Variability in Responses  

  • The presenter mentions that about a quarter of the studies show no effects of exercise on tumor growth. Additionally, in about 10% of the studies, the tumors in the exercise group grow more quickly. In other words, exercise alone does not eliminate tumors in these studies. 

Exercise as Mono Therapy  

  • It is emphasized that exercise, as a single agent or mono therapy treatment, is not expected to cure cancer. The best-case scenarios from these studies involve slowing the progression of cancer rather than complete elimination. 

Mechanisms for Improved Responses  

  • The presenter explains that exercise improves the response of tumors to drugs, even in scenarios where exercise alone does not show significant effects. The mechanisms for this improvement include enhanced angiogenesis, improved intratumoral vascularization, and increased blood flow into tumors, leading to better drug delivery. 

I think all three presenters presented insightful data. And I am not disputing the scientific fact that obesity is truly a breast cancer risk. The strategies listed by the panelists which include exercise, a controlled diet, and using novel drugs to induce weight loss leads to a healthier society, are all reasonable stances to reduce the risk of breast cancer and improve treatment outcomes for people living with this disease. However, the data presented throughout all presentations showed that America is an obese country. This means obesity is a breast cancer risk factor and the cause of a myriad of other diseases, and given such, this is a public health crisis. However, the method to address this complex matter is still not talked about enough. This is why one of my main concerns—the same as last year—is inequity. 

Obesity, similar to breast cancer, is a complex public health crisis. It is fueled by multiple intersectional causes. For example, how many people have access to a quality fitness trainer? Taking this question a bit further, how many people can afford to pay a fitness and nutritional coach for an individualized lifestyle plan? Food deserts, food swamps, the ongoing climate crisis, economic insecurity, and declining mental and emotional well-being are justice issues that have been linked to obesity in many individuals. This year again, I am reiterating that we need systemic change to address and end not just the obesity crisis but also the breast cancer crisis.