Insulin Resistance May Contribute to Worse Prognosis in Black Women with Breast Cancer

May 16, 2020

Insulin resistance was found to be 1 factor that contributes to the worse prognosis in breast cancer between black and white women, potentially through direct effects of insulin on the tumor insulin receptor.

A study of US women with newly diagnosed invasive breast cancer published in Breast Cancer Research found that insulin resistance is 1 factor that contributes to the worse prognosis in breast cancer between black and white women, potentially through direct effects of insulin on the tumor insulin receptor (IR).1

Given the differences in circulating insulin levels and tumor IR expression between black and white women, the researchers indicated that it will be important in future studies to explore whether lowering insulin levels or targeting IR signaling will improve breast cancer survival disparities. 

“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,” lead author Emily J. Gallagher, MD, PhD, assistant Professor of Medicine at the Icahn School of Medicine at Mount Sinai, said in a press release.2 “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.”

The cross-sectional, multi-center study was conducted across 10 hospitals and recruited self-identified black women and white women with newly diagnosed invasive breast cancer. The primary outcome was to determine if insulin resistance, which was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR), mediated the effect of race on prognosis using the multivariate linear mediation model.

Of the 515 women recruited, 83% were white women and 17% were black women. Overall, the metabolic syndrome of insulin resistance was found to be more prevalent in black women than in white women (40% vs 20%; P < 0.0001). Moreover, HOMA-IR was higher in black women than in white women (1.9 ± 1.2 vs 1.3 ± 1.4; P = 0.0005). 

Poor breast cancer prognosis was also found to be more prevalent in black women than in white women (28% vs 15%; P = 0.004). Even further, HOMA-IR was positively associated with NPI score (r = 0.1; P = 0.02). 

The mediation model, adjusted for age, demonstrated that HOMA-IR significantly mediated the correlation between black race and poor prognosis (β = 0.04, 95% CI 0.005-0.009, P = 0.002). In addition, IR expression was higher in tumors from black women than in those from white women (79% vs 52%, p = 0.004), and greater IR/insulin growth factor 1 receptor [IGF-1R] ratio was also associated with higher NPI score (IR/IGF-1R > 1: 4.2 ± 0.8 vs IR/IGF-1R = 1: 3.9 ± 0.8 vs IR/IGF-1R < 1: 3.5 ± 1.0; P < 0.0001).

“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,” co-senior investigator Nina Bickell, MD, PhD, 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, said in a press release.

Notably, the researchers had incomplete data on some breast cancer risk factors, including reproductive history and parity. Additionally the prevalence of obesity as defined by BMI was lower in this study than expected for a US population. The researchers indicated that this likely to explain the lower than anticipated HOMA-IR results. 

“While the focus of our study was to examine the link between insulin resistance and disparities in prognosis in women with newly diagnosed breast cancer, we acknowledge that this is certainly just one of a number of complex factors that contribute to racial disparities in breast cancer prognosis,” the authors wrote.

References:

1. Gallagher EJ, Fei K, Feldman SM, et al. Insulin resistance contributes to racial disparities in breast cancer prognosis in US women. Breast Cancer Research. doi:10.1186/s13058-020-01281-y

2. Insurance Resistance Contributes to Racial Disparities in Breast Cancer Prognosis in U.S. Women, Mount Sinai Researchers Reveal [news release]. New York, NY. Published May 12, 2020. newswise.com/articles/insulin-resistance-contributes-to-racial-disparities-in-breast-cancer-prognosis-in-u-s-women-mount-sinai-researchers-reveal?sc=dwhr&xy=10019792. Accessed May 12, 2020.