Abstract P1-08-10: Insulin resistance and breast cancer incidence and mortality in postmenopausal women
Authors: Chlebowski RT , Pan K , Mortimer J , Cespedes Feliciano EM , Gunter MJ , Hurria A , Rohan T , Vitolins MZ , Adams-Campbell L , Ho G , Cheng T-YD , Nelson R 
Published: May 2019

Abstract
Background:Obese postmenopausal women are at higher breast cancer risk potentially
driven by hyperinsulinemia. However, reports of insulin level associations with breast cancer
incidence and survival are inconsistent. Therefore, we examined associations among insulin
resistance by homeostasis model assessment-insulin resistance (HOMA-IR) index and
incident breast cancer, deaths from breast cancer, and deaths after breast cancer in
postmenopausal women participating in the Women's Health Initiative (WHI).
Patients and Methods:From the 161,808 postmenopausal women, aged 50-79 years,
enrolled at 40 US clinical centers from 1993 through1998 in WHI clinical trials or the
observational study, 22,837 with available fasting serum insulin and glucose by the same
methodology and no prior breast cancer represent the current study population. The
exposure was insulin resistance (HOMA-IR index) as [fasting insulin (qIU/ml) times fasting
glucose (mg/dL) / 22.5. Survival by cause was determined by central medical record or
death certificate review, enhanced by National Death Index queries. Breast cancers, initially
ascertained by serial survey, were confirmed by medical record review. Associations
between HOMA-IR quartiles and breast cancer outcomes were examined using Cox multi-
variate proportional hazards models with results reported as hazard ratios (HR) and 95%
confidence intervals.
Results: At entry, women in the highest HOMA-IR quartile were more likely to be Black,
have lower education level, have higher body mass index (BMI), higher waist circumference
≥ 88 cm and lower physical activity levels, but have lower calculated five-year breast cancer
risk. After 18.1 years median follow-up from randomization with 1,148 incident breast
cancers, breast cancer incidence was higher in women in the highest, compared to the
lowest, HOMA-IR index quartile (HR 1.39 95% CI 1.14 -1.69, P = 0.0012). Of the women
with incident breast cancer, 353 (31%) have died, with cause of death available on 334
(95% of cases) where breast cancer was the most common cause of death (33%); followed
by cardiovascular disease (24%); and other cancers (13%). With median post-breast cancer
diagnosis follow-up of 10.5 years, breast cancer mortality was examined from breast cancer
diagnosis. No association was found between death from breast cancer and HOMA-IR.
However, women with breast cancer in the highest HOMA-IR quartile, compared to women
in the lowest, were significantly more likely to experience death after breast cancer from
any cause (HR 1.45 95% CI 1.00 - 2.09, P = 0.0488) and were at somewhat higher risk of
death from cardiovascular disease (HR 1.51 95% CI 0.67 - 3.41) and other causes (HR 1.93
95% CI 0.87-4.27).
Conclusion:In postmenopausal women, higher insulin resistance is associated with higher
breast cancer incidence and more deaths after breast cancer, likely due to insulin influence
on several causes of death. However, deaths from breast cancer, even in this older
postmenopausal population, remains a major factor limiting survival which needs to be
addressed. The findings suggest insulin resistance represented a potential intervention
target for postmenopausal women with early stage
breast cancer.
Citation Format: Chlebowski RT, Pan K, Mortimer J, Cespedes Feliciano EM, Gunter MJ, Hurria A, Rohan T, Vitolins MZ, Adams-Campbell L, Ho G, Cheng T-YD, Nelson R. Insulin resistance and breast cancer incidence and mortality in postmenopausal women [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-10.