Insulin-like Growth Factor and Mammographic Density in Postmenopausal Norwegian Women

Abstract

Insulin-like growth factor-I (IGF-I) is associated with breast cancer risk among premenopausal women but rarely among postmenopausal women. Recent data from two European studies suggested an increased risk of breast cancer with increasing levels of IGF-I among women >50 years old or among postmenopausal hormone therapy users z55 years old. Mammographic density is one of the strongest risk factors, and possibly an intermediate marker, for breast cancer. We examined the relationship between IGF and mammographic density among postmenopausal women overall and according to hormone therapy use. Altogether, 977 postmenopausal participants in the Norwegian governmental mammographic screening program had IGF concentrations measured by ELISA. Mammograms were classified according to percent and absolute mammographic densities using a previously validated computer-assisted method. After adjustment for age, number of children, age at menopause, body mass index, and hormone therapy use, both plasma IGF-I concentration (P trend = 0.02) and IGF-I/ IGF binding protein 3 ratio (P trend = 0.02) were positively associated with percent mammographic density. The magnitudes of differences in percent mammographic density between women in the lowest and highest quartiles of IGF-I concentrations were 1.5% absolute difference and 21% relative difference. These associations were similar with absolute mammographic density as the outcome variable. When the analyses were stratified according to hormone therapy use, the associations between IGF-I and mammographic density were significant among noncurrent users (P trend = 0.03). In conclusion, we found a positive but weak association between plasma IGF-I concentrations and both percent and absolute mammographic densities among postmenopausal women. These associations were found among noncurrent hormone therapy users but not among current users. (Cancer Epidemiol Biomarkers Prev 2007;16(1):57 -62)

Endogenous sex hormones, prolactin and mammographic density in postmenopausal Norwegian women

“…We have previously shown a positive association between plasma IGF-I concentrations and mammographic density in this study population. 24 Laboratory studies have suggested that IGF-I can both activate and increase the number of estrogen receptors, 20,21 and that the IGF-I-ER activation may be necessary for a maximal estrogen-mediated estrogen receptors activation. 21 In a case-control study among postmenopausal Chinese women, such a synergistic effect between estrone and IGF-I was suggested in relation to breast cancer risk.…”

“…We kept these variables in the multivariate model along with the variables that previously have been found to be associated with mammographic density in this study population. 24,25,29 This procedure left the following factors to be included in the final model: age at screening, number of children, age at menopause, BMI and HT use.…”

“…23 We have previously shown that IGF-I levels are positively associated with mammographic density among the postmenopausal women in this study. 24 The objective of this cross-sectional study was to examine the associations between circulating plasma levels of sex hormones, SHBG and prolactin and mammographic densities among postmenopausal women not currently using HT. We also wanted to examine if IGF-I levels modified the association between estrogen and mammographic density, as has been suggested by laboratory studies.…”

Insulin-like growth factor 1 receptor expression in breast cancer tissue and mammographic density

“…As a factor associated with mammographic breast density, the insulin-like growth factor (IGF) system has been well documented and reported to be of more relevance to premenopausal women (4,5). The IGF system acts as a factor controlling growth in the human body and plays an important role in the development of normal breast tissues.…”

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

“…Insulin-like growth factor-I (IGF-I), a circulating peptide, may be such a factor because its levels are associated with breast cancer risk (3) and it is mitogenic and inhibits apoptosis in breast epithelial cells (4). Despite this biologic plausibility, an association has not been observed between circulating IGF-I concentrations and percent dense area in most studies of postmenopausal women (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). As these studies were cross-sectional, how mammographic density changes as IGF-I levels change has not been examined.…”