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