The overall cancer death rate in the United States is falling, with more than 4.1 million cancer deaths avoided between 1991 and 2021, according to an American Association for Cancer Research report released in September. Yet in the United States, 40 percent of all cancers are associated with modifiable risk factors such as excess body weight, unhealthy dietary patterns, alcohol intake, and physical inactivity.

During the 2024 San Antonio Breast Cancer Symposium^®, panelists will discuss how to improve metabolic health in women with obesity, thereby reducing their risk for breast cancer. Risk Reduction and Early Detection: Mechanisms of Obesity-Related Risk for Breast Cancer and Approaches to Risk Reduction will take place Tuesday, December 10, from noon to 1:45 p.m. CT in Hemisfair Ballroom 1-2 at the Henry B. Gonzalez Convention Center.

“Women at all risk levels can reduce their chance of developing breast cancer and several other cancers with healthy behaviors,” said Carol Fabian, MD, University of Kansas Medical Center, who will be the moderator for the special session. For women at average and moderately increased risk, healthy behaviors along with appropriate screening behaviors may be the only intervention that is needed.

A healthy diet for this population would include five servings of fruits and vegetables per day, whole grains, and minimally processed meat paired with three or more hours of moderate-intensity exercise per week, maintaining a healthy weight, and minimizing alcohol intake. These lifestyle modifications can reduce risk of breast cancer by about 30 percent, along with common health problems such as diabetes and heart disease, yet fewer than 20 percent of Americans achieve these goals, Dr. Fabian noted.  

For the 40 percent or more of adult women who have developed obesity, a 10 percent reduction in weight (about 20 percent reduction in body fat) may be necessary to reduce breast cancer risk. Achieving and maintaining that level of loss is challenging, as is any long-term behavioral modification, particularly for individuals who may be genetically predisposed to hold on to those calories, she continued. Consequently, many women are turning to pharmacotherapy for help with weight loss and maintenance. But what do we know about these newer agents for weight loss and cancer risk?

Panelists will address lifestyle, genetic, and epigenetic interactions in predicting development of obesity and response to calorie restriction and physical activity; how fat loss and metabolic improvement affect cancer risk; and the impact of types of exercise and pharmacotherapy, including nutrient-stimulated hormone (NUSH)-based therapeutics. The NUSH-based therapeutics include drugs with glucagon-like peptide-1 (GLP-1) +/- glucose-dependent insulinotropic polypeptide (GIP) receptor agonist properties.

For women at higher risk of developing breast cancer, especially those currently in a metabolically normal range, additions to healthy behaviors may be desirable. However, women are reluctant to take a drug with potential side effects for a disease that they may not have. These concerns have been a significant challenge to breast cancer risk reduction through pharmacotherapy.

“We are addressing this by testing lower doses of drugs like tamoxifen, which has been found to minimize side effects but reduces risk for breast cancer by about two-thirds in postmenopausal women,” Dr. Fabian said. “However, risk reduction in premenopausal women was much less and not significant.”

Consequently, current early-phase trials are looking into which premenopausal women might benefit from lower doses.

“We are also beginning to accept that women without cancer are likely to take risk-reducing agents over a protracted period of time if they address other ongoing symptoms or problems such that they improve rather than adversely impact quality of life,” Dr. Fabian said.

Interventions such as metformin used to correct metabolic dysfunction, combinations of selective estrogen receptor modulators (SERMs) and low-dose estrogen for peri- and post-menopausal women with vasomotor symptoms or the NUSH agents discussed earlier are all being studied for their effects on risk for breast cancer.  

Not having an easily accessed quantifiable and objectively measured biomarker that can predict outcome from an intervention has also been an obstacle to breast cancer prevention.

“Heart disease has LDL cholesterol, type 2 diabetes has A1C, but breast cancer risk? To some extent, the new fully automated measures of change in area or volume of mammographic density is serving as a biomarker of response to SERMS like tamoxifen in clinical trials, but it may be premature to use this as an individual assessment of response,” Dr. Fabian said. “Reversible blood biomarkers of risk, such as circulating miRNA, would also be most helpful.”

In the future, a variety of affordable interventions that are life phase and risk appropriate, and which address other common symptoms or problems, will be available for breast cancer risk reduction. These will be paired with easy-to-perform tests measuring biomarkers associated with risk/response, she explained.