Metabolic syndrome, insulin resistance, and mammographic density in pre- and postmenopausal women

Abstract

Little is known about the association of metabolic syndrome (MetS) or insulin resistance (IR) with mammographic density, a strong risk factor for breast cancer. The goal of this study was to evaluate these associations in pre- and postmenopausal women. A cross-sectional study was performed in 73,974 adult women who underwent a comprehensive health screening examination that included a mammogram between 2011 and 2013 (mean age 42.6 years). MetS was defined according to the modified National Cholesterol Education Program Adult Treatment Panel III. IR was assessed with the homeostasis model assessment-insulin resistance (HOMA-IR). Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for dense breast were estimated using logistic regression models after adjustment for potential confounders. In premenopausal women, MetS and all its components except waist circumference were associated with dense breast. After adjustment for potential confounders, the OR (95% CI) for dense breast in women with MetS compared with those without MetS was 1.22 (1.06-1.39). In postmenopausal women, however, there was positive but non-significant association between MetS and dense breast. In both pre- and postmenopausal women, high blood glucose and IR were positively associated with dense breast. The OR (95% CI) for dense breast between the highest and lowest quartiles of HOMA-IR was 1.29 (1.20-1.39) for premenopausal women and 1.44 (1.05-1.97) for postmenopausal women. In a large sample of Korean women, MetS and IR were associated with mammographic dense breast, demonstrating that IR, a potentially modifiable risk factor, may increase breast cancer risk, possibly through high mammographic density.

Mammographic breast density, its changes, and breast cancer risk in premenopausal and postmenopausal women

“…This association was similar in premenopausal and postmenopausal women but did not reach statistical significance. In a sensitivity analysis when dense breasts were differently defined as only "extremely dense," 24 the association between persistent dense breasts and breast cancer risk was consistently observed (see Supporting Table 3). When analyses were restricted to participants who remained premenopausal throughout the follow-up period, persistent dense breasts were associated with an increased risk of breast cancer (see Supporting Table 4).…”

“…In our sensitivity analysis of changes in breast density and breast cancer risk, dense breasts were defined differently as only "extremely dense," which also has been used in other studies. 24 We performed all analyses in premenopausal and postmenopausal women. Likelihood ratio tests were used to test interactions by menopausal status comparing models with and without multiplicative interaction terms.…”

“…2). 3,24 Incident Breast Cancer Cases Breast cancer cases were identified through self-reporting of physician-diagnosed breast cancer using standardized, self-administered questionnaires at the time of follow-up visits. 20 When compared with confirmed invasive breast cancer (International Classification of Diseases, Tenth Revision [ICD-10] codes C50.0-C50.9) in the national cancer registry data in a subsample of 25,873 participants, the sensitivity and specificity for the self-reporting of physician-diagnosed breast cancer were 97.1% and 99.1%, respectively.…”

Diagnostic and prognostic significance of serum apolipoprotein C-I in triple-negative breast cancer based on mass spectrometry

“…64 Emerging roles of apoC-III synthesized in the liver, and to a minor degree, small intestine, include directing the atherogenicity of high-density lipoprotein, intestinal dietary triglyceride trafficking and modulating insulinsecreting pancreatic b-cell survival and apoptosis via activation of the mitogen-activated protein kinase (MAPK) p38 and extracellular signal regulated protein kinases 1 and 2 (ERK1/2), 65,66 resulting in hyperglycemia, positive effects on proliferation and colony formation ability of BC cells, and high mammographic density-induced BC risk due to hypoinsulinemia. 67,68 An earlier study by Moore and colleagues provided evidence that common functional variations at the APOC1 gene locus increase susceptibility to renal cell carcinoma. 69 Takano et al 70 compared preand postoperative serum protein profiles obtained from pancreatic cancer patients subjected to curative pancreatectomy using SELDI-TOF-MS, and identified 6420 and 6630 Da proteins as apoC-I, which correlated with poor prognosis.…”

The Short-Term Effect of Weight Loss Surgery on Volumetric Breast Density and Fibroglandular Volume

“…Weight loss surgery not only results in a drastic reduction in BMI but also often reverses diabetes and many components of the metabolic syndrome [21, 22]. Metabolic syndrome and insulin resistance are associated with mammographic dense breasts [23]. In most patients, WLS causes a significant reduction in body fat, which is expected to increase breast density due to the inverse relationship of mammographic density with BMI [24].…”