TY - JOUR
T1 - Insulin resistance contributes to racial disparities in breast cancer prognosis in US women
AU - Gallagher, Emily J.
AU - Fei, Kezhen
AU - Feldman, Sheldon M.
AU - Port, Elisa
AU - Friedman, Neil B.
AU - Boolbol, Susan K.
AU - Killelea, Brigid
AU - Pilewskie, Melissa
AU - Choi, Lydia
AU - King, Tari
AU - Nayak, Anupma
AU - Franco, Rebeca
AU - Cruz, Daliz
AU - Antoniou, Irini M.
AU - Leroith, Derek
AU - Bickell, Nina A.
N1 - Publisher Copyright:
© 2020 The Author(s).
PY - 2020/5/12
Y1 - 2020/5/12
N2 - 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). Conclusions: In this multi-center, cross-sectional study of US women with newly diagnosed invasive breast cancer, insulin resistance is one factor mediating part of the association between race and poor prognosis in breast cancer.
AB - 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). Conclusions: In this multi-center, cross-sectional study of US women with newly diagnosed invasive breast cancer, insulin resistance is one factor mediating part of the association between race and poor prognosis in breast cancer.
KW - Breast cancer
KW - Cross-sectional study
KW - Disparities
KW - Insulin receptor
KW - Insulin resistance
KW - Insulin-like growth factor receptor
KW - Prognosis
UR - http://www.scopus.com/inward/record.url?scp=85084606046&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85084606046&partnerID=8YFLogxK
U2 - 10.1186/s13058-020-01281-y
DO - 10.1186/s13058-020-01281-y
M3 - Article
C2 - 32393319
AN - SCOPUS:85084606046
SN - 1465-5411
VL - 22
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - 40
ER -
