Insulin Resistance Contributes to Racial Disparities in Breast Cancer Prognosis in U.S. Women, Mount Sinai Researchers Reveal
New study identifies that differences in insulin resistance can explain in part the disparities in breast cancer survival between black and white women
In a new multi-center study of U.S. women with newly diagnosed invasive breast cancer, Mount Sinai researchers have shown that insulin resistance is one factor mediating part of the association between race and poor prognosis in the disease. The findings were published in Breast Cancer Research on Tuesday, May 12.
Despite improvements in breast cancer diagnosis and treatment, black women with breast cancer continue to have worse prognoses on average than white women. Breast cancer prognoses also tend to be worse in patients with insulin resistance, a common condition that occurs when metabolic cells in the body don’t respond adequately to insulin, causing the pancreas to make more insulin to maintain normal glucose levels. Insulin resistance is an important component of obesity, prediabetes, and type 2 diabetes. Patients with these conditions also tend to have more aggressive breast cancer subtypes and increased mortality.
“Given that obesity and diabetes epidemics disproportionately affect minority populations, it is important to understand the relationship of hyperinsulinemia, insulin resistance, and increased insulin receptor (IR) signaling on the progression of breast cancer,” explained lead author Emily J. Gallagher, MD, PhD, Assistant Professor of Medicine (Endocrinology, Diabetes and Bone Disease) at the Icahn School of Medicine at Mount Sinai. Dr. Gallagher specializes in onco-endocrinology, the treatment of endocrine complications of oncology treatments. “Understanding these relationships could explain the different patterns of disease seen in different racial groups and help to identify patients who would benefit from targeted therapy,” she says.
This is the first cross-sectional study to examine in detail insulin resistance as a factor associated to the disparities in breast cancer prognosis between black women and white women. The study included 515 women with a newly diagnosed breast cancer; about 83 percent of the subjects were white and 17 percent black. The Mount Sinai team evaluated the women for insulin resistance, metabolic syndrome—a cluster of conditions that occur together and may include high blood pressure or high blood sugar—and obesity to investigate whether insulin is a key mechanistic link in the association between these metabolic conditions and breast cancer aggressiveness. Samples of breast cancer tissue were examined to assess the role of insulin receptor and insulin-like growth factor receptor expression in disparities in breast cancer prognoses between the racial groups.
The researchers found that insulin resistance was more prevalent in black women with invasive breast cancer than in white women and that insulin resistance mediated part of the effect of race on prognosis. Additionally, the team found that tumors from black women had a higher expression of the insulin receptor, which is what insulin binds to in the tumors. Tumors with a worse prognosis had higher expression of the insulin receptor.
“Our results raise a number of questions for future research and patient care. It will be important in future studies to explore whether lowering insulin levels or targeting IR signaling will improve breast cancer disparities,” said co-senior investigator Nina Bickell, MD, MPH, Associate Director of Community Engaged and Equity Research of The Tisch Cancer Institute and Co-Director of the Center for Health Equity and Community Engaged Research at the Icahn School of Medicine at Mount Sinai.
Derek LeRoith, MD, PhD, Professor of Medicine (Endocrinology, Diabetes and Bone Disease) at the Icahn School of Medicine at Mount Sinai, is also a senior investigator in this research.
The study was supported by grants from the National Cancer Institute at the National Institutes of Health.
About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, over 400 outpatient practices, nearly 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time — discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. We are consistently ranked by U.S. News & World Report's Best Hospitals, receiving high "Honor Roll" status, and are highly ranked: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. U.S. News & World Report’s “Best Children’s Hospitals” ranks Mount Sinai Kravis Children's Hospital among the country’s best in several pediatric specialties. The Icahn School of Medicine at Mount Sinai is one of three medical schools that have earned distinction by multiple indicators: It is consistently ranked in the top 20 by U.S. News & World Report's "Best Medical Schools," aligned with a U.S. News & World Report "Honor Roll" Hospital, and top 20 in the nation for National Institutes of Health funding and top 5 in the nation for numerous basic and clinical research areas. Newsweek’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.