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Background: Insulin resistance is associated with higher all-cause and cancer-specific mortality in postmenopausal women. However, to the authors' knowledge, information regarding insulin resistance and breast cancer mortality risk is limited. Therefore, the authors examined associations between insulin resistance and breast cancer incidence and mortality in a subsample of Women's Health Initiative participants., Methods: A total of 22,837 postmenopausal women with fasting baseline glucose and insulin levels were followed for incident breast cancer and breast cancer mortality. Breast cancers were verified by medical record review and serial National Death Index linkage-enhanced mortality findings. Insulin resistance was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR). Multivariable Cox proportional hazards models were used to compute hazard ratios (HRs) with 95% confidence intervals (95% CIs) for quartile comparisons. Outcomes included breast cancer incidence, deaths from breast cancer, and deaths after breast cancer (breast cancer followed by death from any cause)., Results: During a median of 19.8 years of follow-up of 1328 breast cancer cases, there were 512 deaths reported, 151 of which were from breast cancer. Breast cancer incidence was higher in women in the highest HOMA-IR quartile (HR, 1.34; 95% CI, 1.12-1.61 [P for trend = .003]). Although HOMA-IR was not found to be associated with risk of death from breast cancer (HR, 1.04; 95% CI, 0.60-1.79), women in the highest versus those in the lowest HOMA-IR quartile were at a higher risk of death after breast cancer (HR, 1.78; 95% CI, 1.32-2.39 [P for trend <.001])., Conclusions: Higher levels of insulin resistance in postmenopausal women are associated with higher breast cancer incidence and higher all-cause mortality after breast cancer., (© 2020 American Cancer Society.)

Background: Insulin resistance has been proposed as a mediator of the increased cancer incidence and mortality associated with obesity. However, prior studies included limited cancer deaths and had inconsistent findings. Therefore, we evaluated insulin resistance and cancer-specific and all-cause mortality in postmenopausal women participating in the Women's Health Initiative (WHI)., Methods: Eligible were a subsample of 22 837 WHI participants aged 50-79 years enrolled at 40 US clinical centers from 1993 to 1998 who had baseline fasting glucose and insulin levels. Baseline insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR). Cancers were verified by central medical record review and deaths verified by medical record and death certificate review enhanced by National Death Index queries. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific and all-cause mortality. All statistical tests were two-sided., Results: During a median of 18.9 years of follow-up, 1820 cancer deaths and 7415 total deaths occurred. Higher HOMA-IR quartile was associated with higher cancer-specific mortality (Q4 vs Q1, HR = 1.26, 95% CI = 1.09 to 1.47; Ptrend = .003) and all-cause mortality (Q4 vs Q1, HR = 1.63, 95% CI = 1.51 to 1.76; Ptrend < .001). A sensitivity analysis for diabetes status did not change findings. Among women with body mass index less than 25 kg/m2, higher HOMA-IR quartile was associated with higher cancer mortality (Fine and Gray, P = .004)., Conclusions: High insulin resistance, as measured by HOMA-IR, identifies postmenopausal women at higher risk for cancer-specific and all-cause mortality who could potentially benefit from early intervention., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Few studies have examined the relationship between cardiometabolic risk factors linked to metabolic syndrome and mortality among women with breast cancer., Methods: We used the Women's Health Initiative to evaluate the relationship between cardiometabolic risk factors, including waist circumference (WC), blood pressure, cholesterol level, and presence of type 2 diabetes, and their relation with death from breast cancer, cardiovascular disease (CVD), and other causes among 8641 women with local or regional stage invasive breast cancer. Cox proportional hazards models were used to estimate hazard ratios, and 95% confidence intervals, adjusted for important predictors of survival., Results: After a median of 11.3 years, there were 2181 total deaths, 619 (28.4%) of which were due to breast cancer. Most participants (55.7%) had at least 2 cardiometabolic risk factors, and 4.9% had 3 or 4. Having a larger number of risk factors was associated with higher risk of CVD and other-cause mortality (P trend < .001 for both), but not with breast cancer mortality (P trend = .86). Increased WC was associated with a higher risk of CVD (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.05-1.57) and other-cause mortality (HR, 1.32; 95% CI, 1.16-1.49) and only with a small and nonsignificant higher risk of breast cancer mortality (HR, 1.19; 95% CI, 0.93-1.52). The results did not differ in analyses stratified by race, hormone receptor status, or after an analysis of cases diagnosed within 5 years after baseline., Conclusions: Among women with early stage breast cancer, cardiometabolic risk factors are significantly associated with cardiovascular and other-cause mortality, but not breast cancer mortality. Cancer 2018;124:1798-807. © 2018 American Cancer Society., (© 2018 American Cancer Society.)