Does insulin resistance contribute to the racial disparities that persist in breast cancer prognosis? Researchers at The Tisch Cancer Institute recently explored that question in a cross-sectional study of 515 women in 10 U.S. hospitals on the East Coast and in Michigan, which was published in Breast Cancer Research. They found that it does.

“Our study of U.S. women with newly diagnosed invasive breast cancer found that insulin resistance is a key factor mediating part of the association between race and poor disease prognosis,” says the study’s lead author, Emily Gallagher, MD, PhD, Assistant Professor of  Medicine (Endocrinology, Diabetes and Bone Disease), Icahn School of Medicine at Mount Sinai. “High insulin levels, which are more common in African American women than white women, potentially cause changes within tumor cells that contribute to their survival and more aggressive behavior.”

Rather than being a discrete disease, metabolic syndrome is a set of biological factors in which the body ramps up its insulin production to compensate for the resistance of tissues to insulin that is being made naturally. Past studies have shown that metabolic syndrome is responsible for increased risk of a number of pathologies, including breast cancer. Black women, who experience 39 percent higher rates of breast cancer mortality than white women, are 20 percent more likely to have metabolic syndrome.

Access to good health care and cancer screenings, as well as lifestyle choices and the role of epigenetic and genetic variants, have all been suggested to account for the disparities among races in breast cancer mortality. The Mount Sinai study shows there is also a metabolic rationale for those differences. The team sees its findings as an interim step that could provide an important springboard for further research.

“We learned that breast cancers in Black women have an elevated insulin receptor to insulin-like growth factor 1 receptor ratio,” says the study’s senior author Nina Bickell, MD, Professor, Population Health Science and Policy, Icahn School of Medicine at Mount Sinai. “These findings indicate that Black women are not only more likely to have hyperinsulinemia, but are more susceptible to the tumor-promoting effects of elevated insulin through tumor insulin receptor signaling.”

The research further suggests that insulin resistance may be related to differences in insulin metabolism among races. Previous studies have found that African American women have higher circulating insulin levels than European American women due to reduced hepatic insulin clearance.

“It’s possible that Black women may have long-term exposure to high circulating insulin levels and that these levels may contribute to the development of breast cancer subtypes that carry a poor prognosis,” according to Dr. Bickell.

Based on these findings, the Mount Sinai researchers say it will be important to explore whether lowering insulin levels or targeting insulin receptor signaling can improve breast cancer survival.

“There are many younger Black women in their 40s and 50s with more aggressive types of breast cancer, and that demographic underscores the importance of preventive action,” says Dr. Gallagher. “We should think about improving awareness and identifying people who are at highest risk, then examining how we can intervene to improve their health for the years ahead.”