Longitudinal Changes in IGF-I and IGFBP-3, and Mammographic Density among Postmenopausal Women

Abstract

A relation between the breast cancer risk factors, insulin-like growth factor-I (IGF-I) and mammographic density, is biologically plausible, but results from cross-sectional epidemiologic studies have been mixed. Our objective was to examine the relation in a longitudinal manner, that is, between the change in circulating IGF-I concentrations and the change in mammographic measures over one year. Data from an exercise intervention trial conducted in 302 postmenopausal women ages 50 to 74 years were used. Blood drawn at baseline and postintervention was assessed for IGF-I and its binding protein (IGFBP-3) by direct chemiluminscent immunoassay. Area and volumetric measurements of mammographic dense fibroglandular and nondense fatty tissue were made. Statistical analyses were based on multiple linear regression. A one SD (20.2 ng/mL) change in IGF-I over one year was associated with small changes in percent dense area [mean: 0.8%; 95% confidence interval (CI), 0.1-1.4] and dense area (mean: 1.2 cm 2 ; 95% CI, 0.2-2.1). Change in IGFBP-3 was also associated with percent and absolute dense area. Absolute and percent dense volume, and mammographic measures representing fatty tissue (nondense area and volume) were not associated with changes in IGF-I and IGFBP-3. Longitudinal associations may be more detectable than cross-sectional associations due to the absence of confounding by invariant personal factors. Absolute and percent dense area, measures that are related to breast cancer risk, may be affected by IGF-I. Confirmation should be sought in further longitudinal studies in which larger changes in the IGF system are evoked. Cancer Epidemiol Biomarkers Prev; 22(11); 2116-20. Ó2013 AACR.

An intergenic risk locus containing an enhancer deletion in 2q35 modulates breast cancer risk by deregulating IGFBP5 expression

“…IGFBP5 and 2q35 have both been consistently implicated in cancer, though little was known about the nature of their interaction. Molecular studies of IGFBP5 have revealed its essential role in normal mammary epithelial development (7,8,16,17), contributing to the documented involvement of the IGF signalling axis in mammary density as a risk factor for breast cancer (18)(19)(20). A recent contemporaneous study describes a neighbouring 2q35 breast cancer-associated variant nearby the locus we describe.…”

Assessment of mammographic breast density after sleeve gastrectomy

“…Several mechanisms including metabolic and endocrine changes have been linked to dense breast tissue including cycling estrogen, elevated glucose and insulin resistance, and insulin-like growth factor 1 (IGF-1). (17–19) Interestingly, reduced adiposity following metabolic surgery may be the link between these two groups of phenomena. Not surprisingly, estrogens and inflammatory cytokines produced by adipose tissue have been proposed as a mechanism whereby obesity may be associated with postmenopausal breast cancer.…”

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

“…There have been no published studies reporting the impact of WLS on breast density and whether both components that comprise density, i.e., the fibroglandular tissue and the adipose tissue, are affected. WLS is likely to change both these components that make up density, due to changes in growth factors and hormones such as insulin-like growth factor-1 (IGF-1), and estrogen levels after surgery [ 25 – 27 ]. With improvements in metabolic regulation after WLS, changes in the fibroglandular compartment of the breast may also significantly contribute to the reduction in breast cancer risk.…”