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 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.

scholarly journals Prognostic Impact of Pregnancy After Breast Cancer According to Estrogen Receptor Status: A Multicenter Retrospective Study

2013 ◽  
Vol 31 (1) ◽  
pp. 73-79 ◽  
Author(s):  
Hatem A. Azim ◽  
Niels Kroman ◽  
Marianne Paesmans ◽  
Shari Gelber ◽  
Nicole Rotmensz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Pregnancy Outcome ◽  
Estrogen Receptor Status ◽  
Disease Free Survival ◽  
Prognostic Impact ◽  
Er Positive ◽  
The Impact ◽  
Disease Free ◽  
Er Status

Purpose We questioned the impact of pregnancy on disease-free survival (DFS) in women with history of breast cancer (BC) according to estrogen receptor (ER) status. Patients and Methods A multicenter, retrospective cohort study in which patients who became pregnant any time after BC were matched (1:3) to patients with BC with similar ER, nodal status, adjuvant therapy, age, and year of diagnosis. To adjust for guaranteed time bias, each nonpregnant patient had to have a disease-free interval at least equal to the time elapsing between BC diagnosis and date of conception of the matched pregnant one. The primary objective was DFS in patients with ER-positive BC. DFS in the ER-negative cohort, whole population, and overall survival (OS) were secondary objectives. Subgroup analyses included DFS according to pregnancy outcome and BC–pregnancy interval. With a two-sided α = 5% and β = 20%, 645 ER-positive patients were required to detect a hazard ratio (HR) = 0.65. Results A total of 333 pregnant patients and 874 matched nonpregnant patients were analyzed, of whom 686 patients had an ER-positive disease. No difference in DFS was observed between pregnant and nonpregnant patients in the ER-positive (HR = 0.91; 95% CI, 0.67 to 1.24, P = .55) or the ER-negative (HR = 0.75; 95% CI, 0.51 to 1.08, P = .12) cohorts. However, the pregnant group had better OS (HR = 0.72; 95% CI, 0.54 to 0.97, P = .03), with no interaction according to ER status (P = .11). Pregnancy outcome and BC–pregnancy interval did not seem to impact the risk of relapse. Conclusion Pregnancy after ER-positive BC does not seem to reduce the risk of BC recurrence.

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 Evolution of Estrogen Receptor Status from Primary Tumors to Metastasis and Serially Collected Circulating Tumor Cells

2020 ◽  
Vol 21 (8) ◽  
pp. 2885 ◽  
Author(s):  
Carina Forsare ◽  
Pär-Ola Bendahl ◽  
Eric Moberg ◽  
Charlotte Levin Tykjær Jørgensen ◽  
Sara Jansson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Estrogen Receptor Status ◽  
Metastatic Breast ◽  
Primary Tumors ◽  
Er Positive ◽  
Er Status

Background: The estrogen receptor (ER) can change expression between primary tumor (PT) and distant metastasis (DM) in breast cancer. A tissue biopsy reflects a momentary state at one location, whereas circulating tumor cells (CTCs) reflect real-time tumor progression. We evaluated ER-status during tumor progression from PT to DM and CTCs, and related the ER-status of CTCs to prognosis. Methods: In a study of metastatic breast cancer, blood was collected at different timepoints. After CellSearch® enrichment, CTCs were captured on DropMount slides and evaluated for ER expression at baseline (BL) and after 1 and 3 months of therapy. Comparison of the ER-status of PT, DM, and CTCs at different timepoints was performed using the McNemar test. The primary endpoint was progression-free survival (PFS). Results: Evidence of a shift from ER positivity to negativity between PT and DM was demonstrated (p = 0.019). We found strong evidence of similar shifts from PT to CTCs at different timepoints (p < 0.0001). ER-positive CTCs at 1 and 3 months were related to better prognosis. Conclusions: A shift in ER-status from PT to DM/CTCs was demonstrated. ER-positive CTCs during systemic therapy might reflect the retention of a favorable phenotype that still responds to therapy.

Effect of Dietary Intake of Phytoestrogens on Estrogen Receptor Status in Premenopausal Women With Breast Cancer

2005 ◽  
Vol 51 (2) ◽  
pp. 162-169 ◽  
Author(s):  
Marina S. Touillaud ◽  
Patricia C. Pillow ◽  
Jelena Jakovljevic ◽  
Melissa L. Bondy ◽  
S. Eva Singletary ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Dietary Intake ◽  
Estrogen Receptor Status ◽  
Premenopausal Women ◽  
Receptor Status

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.

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