Insulin resistance contributes to racial disparities in breast cancer prognosis in US women

Abstract

Background: Racial disparities in breast cancer survival between Black and White women persist across all stages of breast cancer. The metabolic syndrome (MetS) of insulin resistance disproportionately affects more Black than White women. It has not been discerned if insulin resistance mediates the link between race and poor prognosis in breast cancer. We aimed to determine whether insulin resistance mediates in part the association between race and breast cancer prognosis, and if insulin receptor (IR) and insulin-like growth factor receptor (IGF-1R) expression differs between tumors from Black and White women. Methods: We conducted a cross-sectional, multi-center study across ten hospitals. Self-identified Black women and White women with newly diagnosed invasive breast cancer were recruited. 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. Demographic data, anthropometric measurements, and fasting blood were collected. Poor prognosis was defined as a Nottingham Prognostic Index (NPI) > 4.4. Breast cancer pathology specimens were evaluated for IR and IGF-1R expression by immunohistochemistry (IHC). Results: Five hundred fifteen women were recruited (83% White, 17% Black). The MetS was more prevalent in Black women than in White women (40% vs 20%, p < 0.0001). 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 more prevalent in Black women than in White women (28% vs 15%. p = 0.004). HOMA-IR was positively associated with NPI score (r = 0.1, p = 0.02). The mediation model, adjusted for age, revealed that HOMA-IR significantly mediated the association between Black race and poor prognosis (β = 0.04, 95% CI 0.005-0.009, p = 0.002). IR expression was higher in tumors from Black women than in those from White women (79% vs 52%, p = 0.004), and greater IR/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).

Consumption of sugar‐sweetened and artificially sweetened beverages and breast cancer survival

“…High SSB consumption increases postprandial blood glucose and insulin levels 40 . Substantial evidence suggests a possible link between hyperglycemia and hyperinsulinemia and a poorer breast cancer prognosis 7,8,13 . In nondiabetic women with breast cancer, 15 high levels of circulating insulin (>13 µIU/mL) before breast cancer treatment were associated with worse disease progression.…”

“…Sugar‐sweetened beverages (SSBs), such as soft drinks, fruit‐flavored drinks, punches, sports drinks, and energy drinks, are among major sources of added sugar in the American diet and can lead to a higher risk of many conditions, including insulin resistance, obesity, type 2 diabetes, and cardiovascular diseases 1‐6 . These conditions may contribute to a poor prognosis among women with breast cancer 7‐14 . High levels of insulin at time of diagnosis have been associated with a worse prognosis in nondiabetic women with breast cancer 15 .…”

Obesity, Type 2 Diabetes, and Cancer Risk

“…In addition to cancer incidence, insulin resistance has been associated with both an increased risk of all-cause mortality and cancer-specific mortality in postmenopausal women ( 55 ). Insulin resistance has been further identified as a factor mediating the relationship between race and poor breast cancer prognosis ( 56 ). In a recent cross-sectional study, self-identified Black women showed greater insulin resistance and poorer prognosis for breast cancer compared to White women ( 56 ).…”

“…Insulin resistance has been further identified as a factor mediating the relationship between race and poor breast cancer prognosis ( 56 ). In a recent cross-sectional study, self-identified Black women showed greater insulin resistance and poorer prognosis for breast cancer compared to White women ( 56 ). It is however, important to note that multiple factors including socio-economic status, environmental exposures, access to healthcare, tumor biology, genetic susceptibility and systemic metabolism can all potentially contibute to the racial disparities in cancer mortality ( 57 ).…”

Prognostic Value of Metabolic Activity of the Psoas Muscle Evaluated By Preoperative 18 F- FDG PET-CT in Breast Cancer: A Retrospective Cross-Sectional Study

“…Several studies have revealed that IR measured by various methods other than 18 F-FDG PET-CT was a prognostic factor of breast cancer (12)(13)(14). The 8th edition of the American Joint Committee on Cancer has incorporated biomarkers such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) into anatomic tumor-node-metastasis staging (15).…”