Can dietary strategies like intermittent fasting or time-restricted eating help breast cancer survivors prevent their tumors from recurring? It’s a question researchers at the University of Colorado (CU) Cancer Center are looking to answer with a new study funded by a $3 million R01 grant from the National Cancer Institute.
CU Cancer Center members Paul MacLean, PhD, and Peter Kabos, MD, along with Victoria Catenacci, MD, an associate professor of endocrinology at the CU School of Medicine, received the funds for a study on the impact of obesity on breast cancer, looking specifically to see if intermittent fasting and time-restricted feeding may help prevent risk of recurrence in women who recently completed treatment for breast cancer.
“This is a question that we get from patients all the time — what type of strategies should they take to improve their outcomes both during and after treatment?” Kabos says. “What we’re trying to do is put data behind that answer.”
Found in translation
The study will begin in tumor-bearing animal models, which will be placed on one of two types of diets: time-restricted feeding, where they only are fed within a certain eight- to nine-hour time window each day; and intermittent fasting, where their caloric intake is dramatically reduced for two to three days per week, and they are fed normally on the other days. Whichever strategy is most effective in reducing tumors will then be applied in a pilot study of a behavioral weight loss intervention in human subjects with breast cancer. The pilot study will use the BfitBwell exercise program for cancer survivors at the CU Anschutz Health and Wellness Center as a platform to recruit participants and manage the exercise component and the Colorado Nutrition Obesity Research Center (NORC) Clinical Intervention and Translation Core to oversee delivery of the dietary component of the behavioral weight loss intervention.
“These animals are going to be overweight or obese, similar to some patients who develop breast cancer,” says MacLean, director of the Colorado NORC. “They're going to be on a relatively Western-type diet, which is what most humans are eating. But there are obviously differences between the species. What makes this grant exciting is that we'll have data from preclinical animal studies that will suggest questions and observations we can then translate into the humans to see if what we're finding is relevant to the human condition. Not everything gets translated, but we actually get to test that translation during the period of the award.”
Looking deeper into obesity
Studies show that obesity can lead to higher risk of incidence or recurrence of breast cancer, and as part of their study, MacLean and Kabos are trying to gain a better understanding of the link.
“As the foundation of this grant, we have a hypothesis that there’s an interplay in the tumor microenvironment between large hypertrophic adipocytes and cancer-associated fibroblasts, and that these two different cell types are working together to create a pro-metastatic tumor microenvironment,” MacLean says. “We hypothesize that if we are able to help our patients lose weight and shrink the adipocytes down, make them less inflammatory, we could disrupt that interplay between cancer-associated fibroblasts and these adipocytes and change the microarchitecture in which the tumor resides and improve outcomes.”
A collaboration between the CU Cancer Center, the Anschutz Health and Wellness Center, the Colorado NORC, and the Colorado Clinical and Translational Sciences Institute, the study will look not just at how losing weight might help breast cancer survivors prevent relapse, but if certain dietary weight-loss strategies have additional benefits when it comes to the disease.
“Intermittent fasting and time-restricted feeding are hot topics in the literature right now, and for good reason,” MacLean says. “The question is, are those unique approaches to caloric restriction? Do they have some sort of unique physiological benefit that is different from a standard calorie-restricted diet that somebody would go on? Or are they just easier to maintain and stay on? That’s what we are hoping to better understand.”
“There’s data that shows intermittent fasting reduces the toxicity of chemotherapies,” Kabos adds, “but obesity and metabolic syndrome are part of the setup for breast cancer progression or recurrence. That's what we're really trying to study how to best approach and implement in patients.”
Journey to personalization
At the end of the five-year study, the researchers hope to have another tool in their toolbox for helping women recovering from breast cancer improve their outcomes — and potentially new strategies for cancer prevention and management as well.
“The long-term vision is to personalize health and wellness for all patients with cancer,” Kabos says. “In this case, we're studying women with breast cancer and personalizing that part of their care. It's not just about beneficial outcomes or reducing the recurrence, but how can we personalize and put data behind improving the well-being of each individual?”