Fructosamine and diabetes as predictors of mortality among Hispanic and non-Hispanic white breast cancer survivors

Avonne E Connor,Stephanie D Boone,Nader Rifai,Richard N Baumgartner,Kathy B Baumgartner,Kala Visvanathan

doi:10.1038/s41523-018-0099-x

Abstract

Epidemiologic studies have found that elevated insulin levels and chronic hyperglycemia among breast cancer (BC) survivors are associated with poor prognosis; few of these studies have included Hispanic women in whom diabetes is highly prevalent. We examined the associations between circulating fructosamine-a biomarker of hyperglycemia and blood glucose control, self-reported diabetes, and risk of BC-specific and all-cause mortality among Hispanic and non-Hispanic white (NHW) women diagnosed with invasive BC. A total of 399 BC survivors (96 Hispanic, 303 NHW) contributed baseline data and plasma samples. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariable Cox proportional hazards regression models. After a median follow-up time of 13 years, a total of 134 deaths occurred, of which 56 deaths were from BC. Diabetes was associated with BC-specific (HR, 2.89; 95% CI 1.27–6.60) and all-cause (HR, 2.10; 95% CI 1.24–3.55) mortality. Associations were stronger among women with clinically high fructosamine levels (>285 µmol/L) (BC-specific: HR, 4.25; 95% CI 1.67–10.80; all-cause: HR, 2.32; 95% CI 1.30–4.14) compared to women with normal levels (≤285 µmol/L). In mediation analysis, fructosamine explained 47% of the association between diabetes and all-cause mortality and 41% of BC-specific mortality; the largest attenuation was among Hispanics for all-cause mortality (56%). Our results demonstrate that poor glycemic control explains a large extent of the relationship between diabetes and mortality among women with invasive BC, particularly among Hispanic women. The associations we observed for BC mortality should be confirmed in larger studies of ethnically diverse BC patients.

Highlights

Breast cancer is the leading cause of death among US Hispanic women, only surpassing heart disease within the last decade.[1,2]According to the American Cancer Society, approximately 19,800Hispanic women were diagnosed with breast cancer in the US in 2015, and approximately 2,800 women died from this disease.[2]Evidence from epidemiologic studies primarily conducted in non-Hispanic white (NHW) women suggests that women with Type 2 diabetes and breast cancer may have an increased risk of breast cancer-specific[3,4,5] and all-cause[6,7,8] mortality
Hispanic women with fructosamine levels in quartile 4 were more than four times more likely to die of any cause (HR, 4.44; 95% confidence intervals (CI) 1.26–15.70); while no significant associations were observed among non-Hispanic white (NHW) women in this same risk group
We measured plasma fructosamine for assessment of hyperglycemia among Hispanic and NHW women diagnosed with invasive breast cancer to evaluate the prognostic significance of this biomarker, in addition to self-reported history of diabetes, with all-cause and breast cancer-specific mortality

Summary

Introduction

Breast cancer is the leading cause of death among US Hispanic women, only surpassing heart disease within the last decade.[1,2]According to the American Cancer Society, approximately 19,800Hispanic women were diagnosed with breast cancer in the US in 2015, and approximately 2,800 women died from this disease.[2]Evidence from epidemiologic studies primarily conducted in non-Hispanic white (NHW) women suggests that women with Type 2 diabetes (hereafter referred to as diabetes) and breast cancer may have an increased risk of breast cancer-specific[3,4,5] and all-cause[6,7,8] mortality. Breast cancer is the leading cause of death among US Hispanic women, only surpassing heart disease within the last decade.[1,2]. Hispanic women were diagnosed with breast cancer in the US in 2015, and approximately 2,800 women died from this disease.[2]. Hispanic white (NHW) women suggests that women with Type 2 diabetes (hereafter referred to as diabetes) and breast cancer may have an increased risk of breast cancer-specific[3,4,5] and all-cause[6,7,8] mortality. Few diabetes-breast cancer survival studies have included Hispanic women,[4,9] in whom diabetes is highly prevalent.[10]. In cell cultures hyperinsulinemia and hyperglycemia sequelae have been shown to increase tumor cell proliferation.[12]

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Results

Conclusion