scholarly journals Body shape throughout life and correlations with IGFs and GH

2007 ◽  
Vol 14 (3) ◽  
pp. 721-732 ◽  
Author(s):  
Eva S Schernhammer ◽  
Shelley S Tworoger ◽  
A Heather Eliassen ◽  
Stacey A Missmer ◽  
Jeff M Holly ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Size ◽  
Birth Weight ◽  
Waist Circumference ◽  
Body Shape ◽  
Premenopausal Women ◽  
Premenopausal Breast Cancer ◽  
Igf I ◽  
Size At Age ◽  
Igfbp 3

Both insulin-like growth factors (IGF) and body size have been linked to premenopausal breast cancer risk. However, observational studies of IGF have not been consistent, and they suggest that perhaps earlier levels of IGF might be more strongly related to breast cancer than those measured at mid-age. We therefore sought to explore associations between several measures of body size throughout life and IGF levels in premenopausal women. We examined cross-sectional associations of birth weight, body shape (or somatotype) at ages 5 and 10, body mass index (BMI) at age 18 and adulthood, bra cup size at age 20, adult waist circumference and waist-to-hip ratio (WHR), and attained height with plasma levels of IGF-I, IGF binding protein 3 (IGFBP-3), IGFBP-1, and GH. Participants were 592 healthy premenopausal women aged 34–52 from the Nurses’ Health Study II. Using multiple linear regression, we computed least-square mean hormone levels across the categories of early life anthropometric factors. We observed consistent and strong inverse associations between body shape at various stages in life and IGF levels. Somatotype at ages 5 and 10 was inversely associated with IGF-I (P for difference, < 0.01) and positively with IGFBP-3 measured later in adulthood. Further, comparing women with a BMI ≥ 25 kg/m2 at age 18 vs < 19 kg/m2, similar associations were observed for IGF-I (P for trend, 0.005) and IGFBP-3 (P for trend, 0.01), which were even stronger for BMI at blood collection (BMI< 20 versus BMI ≥ 30, mean IGF-I 254 ng/ml, 95% CI, 239–271 vs 208 ng/ml, 95% CI, 195–222). Both waist circumference and WHR were strongly and inversely related to IGFBP-1 levels (top versus bottom quartile of waist circumference: 14.5 vs 40.0 ng/ml, P for trend 0.0005; WHR: 18.3 vs 39.4 ng/ml, P for trend 0.002), with similar results for bra cup size at age 20 although they did not reach statistical significance. There was no association between height and IGF or GH levels. Birth weight, on the other hand, was weakly positively associated with both IGF-I and IGFBP-1 levels, and inversely with GH. Our results suggest that childhood and adult body size may affect premenopausal breast cancer risk differently than birth weight, through associations with IGF and GH levels.

Premenopausal breast cancer and the association between estrogen receptor status, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and leptin

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 640-640
Author(s):  
J. Eng-Wong ◽  
S. Chang ◽  
S. Hursting ◽  
S. N. Perkins ◽  
N. Núñez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor Status ◽  
Premenopausal Women ◽  
Normal Weight ◽  
Premenopausal Breast Cancer ◽  
Receptor Status ◽  
Igf I ◽  
Er Positive ◽  
Er Status ◽  
Igfbp 3

640 Background: The IGF pathway and leptin are associated with breast cancer risk in premenopausal women. These proteins are implicated in breast carcinogenesis through their interactions with the estrogen pathway, potentially resulting in specific breast cancer histopathologic subtypes. Methods: Pretreatment serum IGF-I, IGFBP-3 and leptin levels were examined in newly diagnosed premenopausal breast cancer cases to determine whether an association with tumor estrogen receptor status exists. Odds ratios were determined by logistic regression analysis. Likelihood ratio tests for interaction with BMI were conducted. Results: One hundred and eight women were evaluated (mean age 42); 82 were ER positive and 26 were ER negative. 62 were normal weight (BMI<25) and 46 were overweight and obese (BMI≥25). Mean IGF-I, IGFBP-3 and leptin levels did not differ between the ER positive and ER negative tumors. No associations were found between IGF-I, IGFBP-3 or leptin and ER status of tumors overall or by subset analysis in normal weight versus overweight and obese individuals. A suggestion that elevated IGFBP-3 was associated with ER-negative disease did not reach statistical significance. Additionally, normal-weight women with ER-negative disease had higher leptin levels than their normal-weight ER-positive counterparts, although we lacked statistical power to detect an effect of BMI on the association between leptin levels and tumor hormone receptor status. Conclusions: This is the first report examining the IGF pathway and leptin in relation to ER status in premenopausal women with newly diagnosed breast cancer. Our small number of cases suggests a number of intriguing findings that should be evaluated in larger studies. Determining links between ER status and IGFBP-3 and leptin may help better define risk factors and potentially appropriate interventions for ER-negative versus ER-positive breast cancer. No significant financial relationships to disclose.

scholarly journals Insulin-like growth factor-I, its binding proteins (IGFBP-1 and IGFBP-3), and growth hormone and breast cancer risk in The Nurses Health Study II

2006 ◽  
Vol 13 (2) ◽  
pp. 583-592 ◽  
Author(s):  
Eva S Schernhammer ◽  
Jeff M Holly ◽  
David J Hunter ◽  
Michael N Pollak ◽  
Susan E Hankinson
Keyword(s):  
Breast Cancer ◽  
Growth Hormone ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Premenopausal Women ◽  
Health Study ◽  
Blood Collection ◽  
Factor I ◽  
Igf I ◽  
Igfbp 3

Earlier data suggest that the relationship between circulating insulin-like growth factor I (IGF-I) levels and breast cancer risk differs according to menopausal status. We evaluated the association between IGF levels as well as the primary regulator of IGF-I production, growth hormone (GH), and breast cancer risk in the Nurses’ Health Study II (NHS II) cohort, a large cohort of primarily premenopausal women. We conducted a case-control study nested within the prospective NHS II cohort. Plasma concentrations of IGF-I, IGF binding protein (IGFBP)-3, IGFBP-1, and GH were measured in blood samples collected between 1996 and 1999. Totally 317 women were identified who had a diagnosis of invasive or in situ breast cancer between the date of blood collection and June 1 2003; 75% of these women were premenopausal at blood collection. To each of the 317 women, two controls were age-matched for a total of 634 controls. We used conditional logistic regression models to estimate the relative risk of breast cancer. Overall, plasma IGF-I, IGFBP-1, IGFBP-3, and GH levels were not associated with breast cancer risk (relative risks, top vs bottom quartile; IGF-I, 0.98, 95% confidence interval (CI), 0.69–1.39; IGFBP-1, 0.95, 95% CI, 0.63–1.41; IGFBP-3, 1.10, 95% CI, 0.78–1.54; GH, 1.09, 95% CI, 0.82–1.46). These risks were similar for premenopausal women of age 45 years or less. Further adjustment for additional breast cancer risk factors did not change these estimates. In conclusion, circulating IGF-I, IGFBP-1, IGFBP-3, and GH levels appear to have no important association with breast cancer risk in a large cohort of premenopausal women.

scholarly journals Randomized Double-Blind 2 × 2 Trial of Low-Dose Tamoxifen and Fenretinide for Breast Cancer Prevention in High-Risk Premenopausal Women

2009 ◽  
Vol 27 (23) ◽  
pp. 3749-3756 ◽  
Author(s):  
Andrea Decensi ◽  
Chris Robertson ◽  
Aliana Guerrieri-Gonzaga ◽  
Davide Serrano ◽  
Massimiliano Cazzaniga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Neoplasms ◽  
Mammographic Density ◽  
Low Dose ◽  
Endometrial Thickness ◽  
Premenopausal Women ◽  
Intraepithelial Neoplasia ◽  
Premenopausal Breast Cancer ◽  
Double Blind ◽  
Igf I

Purpose Tamoxifen and fenretinide are active in reducing premenopausal breast cancer risk and work synergistically in preclinical models. The authors assessed their combination in a two-by-two biomarker trial. Patients and Methods A total of 235 premenopausal women with pT1mic/pT1a breast cancer (n = 21), or intraepithelial neoplasia (IEN, n = 160), or 5-year Gail risk ≥ 1.3% (n = 54) were randomly allocated to either tamoxifen 5 mg/d, fenretinide 200 mg/d, their combination, or placebo. We report data for plasma insulin-like growth factor I (IGF-I), mammographic density, uterine effects, and breast neoplastic events after 5.5 years. Results During the 2-year intervention, tamoxifen significantly lowered IGF-I and mammographic density by 12% and 20%, respectively, fenretinide by 4% and 10% (not significantly), their combination by 20% and 22%, with no evidence for a synergistic interaction. Tamoxifen increased endometrial thickness principally in women becoming postmenopausal, whereas fenretinide decreased endometrial thickness significantly. The annual rate of breast neoplasms (n = 48) was 3.5% ± 1.0%, 2.1% ± 0.8%, 4.7% ± 1.3%, and 5.2% ± 1.3% in the tamoxifen, fenretinide, combination, and placebo arms, respectively, with hazard ratios (HRs) of 0.70 (95% CI, 0.32 to 1.52), 0.38 (95% CI, 0.15 to 0.90), and 0.96 (95% CI, 0.46 to 1.99) relative to placebo (tamoxifen × fenretinide adverse interaction P = .03). There was no clear association with tumor receptor type. Baseline IGF-I and mammographic density did not predict breast neoplastic events, nor did change in mammographic density. Conclusion Despite favorable effects on plasma IGF-I levels and mammographic density, the combination of low-dose tamoxifen plus fenretinide did not reduce breast neoplastic events compared to placebo, whereas both single agents, particularly fenretinide, showed numerical reduction in annual odds of breast neoplasms. Further follow-up is indicated.

scholarly journals Growth hormone-binding protein is directly and IGFBP-3 is inversely associated with risk of female breast cancer

2007 ◽  
Vol 156 (2) ◽  
pp. 187-194 ◽  
Author(s):  
Kalliopi Pazaitou-Panayiotou ◽  
Theodore Kelesidis ◽  
Iosif Kelesidis ◽  
Athina Kaprara ◽  
Jennifer Blakeman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Breast Cancer Risk ◽  
Female Breast Cancer ◽  
Cancer Risk Factors ◽  
Female Breast ◽  
Igf I ◽  
Breast Cancer Risk Factors ◽  
Igfbp 3

Objective: Several components of the GH and IGF systems have been implicated in the development of malignancies. All components of these hormonal systems have never been jointly evaluated in female breast cancer, and previous studies have not examined the role of IGF-binding proteins (IGFBP-4, IGFBP-6) or GH-binding protein (GHBP). Design: Hospital-based case–control study. Methods: In this sample of primarily postmenopausal women, we obtained serum measures of IGF-I, IGF-II, and binding proteins IGFBP-1, IGFBP-3, IGFBP-4, IGFBP-6, as well as GHBP, insulin, and leptin from 74 breast cancer cases and 76 control subjects. Results: In crude analyses, we found lower age-standardized mean IGF-I, IGFBP-3, IGFBP-4, IGFBP-6, and higher IGFBP-1 and GHBP in breast cancer cases when compared with controls. Multivariate models mutually adjusted for other GH–IGF system components and classical breast cancer risk factors demonstrated an inverse association between IGFBP-3 and risk of breast cancer (odds ratio (OR) = 0.2, P < 0.01) and a direct association between GHBP and disease risk (OR = 3.3, P < 0.01). No significant associations were detected in multivariate analyses among IGF-I, IGF-II or IGFBP-1, IGFBP-4, IGFBP-6 with risk of breast cancer, indicating that these factors may not have effects independent of and/or comparable with IGFBP-3 and GHBP. Conclusions: These results support a protective role of IGFBP-3 and demonstrate for the first time an increased risk of breast cancer with higher GHBP, after accounting for variation in IGFs, IGFBPs, and classical breast cancer risk factors.

scholarly journals Body mass index, waist circumference and waist–hip ratio and serum levels of IGF-I and IGFBP-3 in European women

2006 ◽  
Vol 30 (11) ◽  
pp. 1623-1631 ◽  
Author(s):  
I T Gram ◽  
T Norat ◽  
S Rinaldi ◽  
L Dossus ◽  
A Lukanova ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Waist Circumference ◽  
Body Mass ◽  
Serum Levels ◽  
Waist Hip Ratio ◽  
Igf I ◽  
European Women ◽  
Igfbp 3

scholarly journals IGF-I, IGF Binding Protein (IGFBP)-3, Phosphoisoforms of IGFBP-1, and Postnatal Growth in Very Low Birth Weight Infants

2002 ◽  
Vol 87 (5) ◽  
pp. 2171-2179 ◽  
Author(s):  
Eero Kajantie ◽  
Leo Dunkel ◽  
Eeva-Marja Rutanen ◽  
Markku Seppälä ◽  
Riitta Koistinen ◽  
...  
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Very Low Birth Weight ◽  
Binding Protein ◽  
Postnatal Growth ◽  
Low Birth Weight Infants ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3
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