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Circulating insulin-like growth factor-I, insulin-like growth factor binding protein-3 and terminal duct lobular unit involution of the breast: a cross-sectional study of women with benign breast disease
BACKGROUND: Terminal duct lobular units (TDLUs) are the primary structures from which breast cancers and their precursors arise. Decreased age-related TDLU involution and elevated mammographic density are both correlated and independently associated with increased breast cancer risk, suggesting that...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758090/ https://www.ncbi.nlm.nih.gov/pubmed/26893016 http://dx.doi.org/10.1186/s13058-016-0678-4 |
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author | Horne, Hisani N. Sherman, Mark E. Pfeiffer, Ruth M. Figueroa, Jonine D. Khodr, Zeina G. Falk, Roni T. Pollak, Michael Patel, Deesha A. Palakal, Maya M. Linville, Laura Papathomas, Daphne Geller, Berta Vacek, Pamela M. Weaver, Donald L. Chicoine, Rachael Shepherd, John Mahmoudzadeh, Amir Pasha Wang, Jeff Fan, Bo Malkov, Serghei Herschorn, Sally Hewitt, Stephen M. Brinton, Louise A. Gierach, Gretchen L. |
author_facet | Horne, Hisani N. Sherman, Mark E. Pfeiffer, Ruth M. Figueroa, Jonine D. Khodr, Zeina G. Falk, Roni T. Pollak, Michael Patel, Deesha A. Palakal, Maya M. Linville, Laura Papathomas, Daphne Geller, Berta Vacek, Pamela M. Weaver, Donald L. Chicoine, Rachael Shepherd, John Mahmoudzadeh, Amir Pasha Wang, Jeff Fan, Bo Malkov, Serghei Herschorn, Sally Hewitt, Stephen M. Brinton, Louise A. Gierach, Gretchen L. |
author_sort | Horne, Hisani N. |
collection | PubMed |
description | BACKGROUND: Terminal duct lobular units (TDLUs) are the primary structures from which breast cancers and their precursors arise. Decreased age-related TDLU involution and elevated mammographic density are both correlated and independently associated with increased breast cancer risk, suggesting that these characteristics of breast parenchyma might be linked to a common factor. Given data suggesting that increased circulating levels of insulin-like growth factors (IGFs) factors are related to reduced TDLU involution and increased mammographic density, we assessed these relationships using validated quantitative methods in a cross-sectional study of women with benign breast disease. METHODS: Serum IGF-I, IGFBP-3 and IGF-I:IGFBP-3 molar ratios were measured in 228 women, ages 40-64, who underwent diagnostic breast biopsies yielding benign diagnoses at University of Vermont affiliated centers. Biopsies were assessed for three separate measures inversely related to TDLU involution: numbers of TDLUs per unit of tissue area (“TDLU count”), median TDLU diameter (“TDLU span”), and number of acini per TDLU (“acini count”). Regression models, stratified by menopausal status and adjusted for potential confounders, were used to assess the associations of TDLU count, median TDLU span and median acini count per TDLU with tertiles of circulating IGFs. Given that mammographic density is associated with both IGF levels and breast cancer risk, we also stratified these associations by mammographic density. RESULTS: Higher IGF-I levels among postmenopausal women and an elevated IGF-I:IGFBP-3 ratio among all women were associated with higher TDLU counts, a marker of decreased lobular involution (P-trend = 0.009 and <0.0001, respectively); these associations were strongest among women with elevated mammographic density (P-interaction <0.01). Circulating IGF levels were not significantly associated with TDLU span or acini count per TDLU. CONCLUSIONS: These results suggest that elevated IGF levels may define a sub-group of women with high mammographic density and limited TDLU involution, two markers that have been related to increased breast cancer risk. If confirmed in prospective studies with cancer endpoints, these data may suggest that evaluation of IGF signaling and its downstream effects may have value for risk prediction and suggest strategies for breast cancer chemoprevention through inhibition of the IGF system. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-016-0678-4) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4758090 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-47580902016-02-19 Circulating insulin-like growth factor-I, insulin-like growth factor binding protein-3 and terminal duct lobular unit involution of the breast: a cross-sectional study of women with benign breast disease Horne, Hisani N. Sherman, Mark E. Pfeiffer, Ruth M. Figueroa, Jonine D. Khodr, Zeina G. Falk, Roni T. Pollak, Michael Patel, Deesha A. Palakal, Maya M. Linville, Laura Papathomas, Daphne Geller, Berta Vacek, Pamela M. Weaver, Donald L. Chicoine, Rachael Shepherd, John Mahmoudzadeh, Amir Pasha Wang, Jeff Fan, Bo Malkov, Serghei Herschorn, Sally Hewitt, Stephen M. Brinton, Louise A. Gierach, Gretchen L. Breast Cancer Res Research Article BACKGROUND: Terminal duct lobular units (TDLUs) are the primary structures from which breast cancers and their precursors arise. Decreased age-related TDLU involution and elevated mammographic density are both correlated and independently associated with increased breast cancer risk, suggesting that these characteristics of breast parenchyma might be linked to a common factor. Given data suggesting that increased circulating levels of insulin-like growth factors (IGFs) factors are related to reduced TDLU involution and increased mammographic density, we assessed these relationships using validated quantitative methods in a cross-sectional study of women with benign breast disease. METHODS: Serum IGF-I, IGFBP-3 and IGF-I:IGFBP-3 molar ratios were measured in 228 women, ages 40-64, who underwent diagnostic breast biopsies yielding benign diagnoses at University of Vermont affiliated centers. Biopsies were assessed for three separate measures inversely related to TDLU involution: numbers of TDLUs per unit of tissue area (“TDLU count”), median TDLU diameter (“TDLU span”), and number of acini per TDLU (“acini count”). Regression models, stratified by menopausal status and adjusted for potential confounders, were used to assess the associations of TDLU count, median TDLU span and median acini count per TDLU with tertiles of circulating IGFs. Given that mammographic density is associated with both IGF levels and breast cancer risk, we also stratified these associations by mammographic density. RESULTS: Higher IGF-I levels among postmenopausal women and an elevated IGF-I:IGFBP-3 ratio among all women were associated with higher TDLU counts, a marker of decreased lobular involution (P-trend = 0.009 and <0.0001, respectively); these associations were strongest among women with elevated mammographic density (P-interaction <0.01). Circulating IGF levels were not significantly associated with TDLU span or acini count per TDLU. CONCLUSIONS: These results suggest that elevated IGF levels may define a sub-group of women with high mammographic density and limited TDLU involution, two markers that have been related to increased breast cancer risk. If confirmed in prospective studies with cancer endpoints, these data may suggest that evaluation of IGF signaling and its downstream effects may have value for risk prediction and suggest strategies for breast cancer chemoprevention through inhibition of the IGF system. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-016-0678-4) contains supplementary material, which is available to authorized users. BioMed Central 2016-02-18 2016 /pmc/articles/PMC4758090/ /pubmed/26893016 http://dx.doi.org/10.1186/s13058-016-0678-4 Text en © Horne et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Horne, Hisani N. Sherman, Mark E. Pfeiffer, Ruth M. Figueroa, Jonine D. Khodr, Zeina G. Falk, Roni T. Pollak, Michael Patel, Deesha A. Palakal, Maya M. Linville, Laura Papathomas, Daphne Geller, Berta Vacek, Pamela M. Weaver, Donald L. Chicoine, Rachael Shepherd, John Mahmoudzadeh, Amir Pasha Wang, Jeff Fan, Bo Malkov, Serghei Herschorn, Sally Hewitt, Stephen M. Brinton, Louise A. Gierach, Gretchen L. Circulating insulin-like growth factor-I, insulin-like growth factor binding protein-3 and terminal duct lobular unit involution of the breast: a cross-sectional study of women with benign breast disease |
title | Circulating insulin-like growth factor-I, insulin-like growth factor binding protein-3 and terminal duct lobular unit involution of the breast: a cross-sectional study of women with benign breast disease |
title_full | Circulating insulin-like growth factor-I, insulin-like growth factor binding protein-3 and terminal duct lobular unit involution of the breast: a cross-sectional study of women with benign breast disease |
title_fullStr | Circulating insulin-like growth factor-I, insulin-like growth factor binding protein-3 and terminal duct lobular unit involution of the breast: a cross-sectional study of women with benign breast disease |
title_full_unstemmed | Circulating insulin-like growth factor-I, insulin-like growth factor binding protein-3 and terminal duct lobular unit involution of the breast: a cross-sectional study of women with benign breast disease |
title_short | Circulating insulin-like growth factor-I, insulin-like growth factor binding protein-3 and terminal duct lobular unit involution of the breast: a cross-sectional study of women with benign breast disease |
title_sort | circulating insulin-like growth factor-i, insulin-like growth factor binding protein-3 and terminal duct lobular unit involution of the breast: a cross-sectional study of women with benign breast disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758090/ https://www.ncbi.nlm.nih.gov/pubmed/26893016 http://dx.doi.org/10.1186/s13058-016-0678-4 |
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