Article Data

  • Views 277
  • Dowloads 136

Original Research

Open Access

Possible effects of insulin-like growth factor-I, IGF-binding protein-3 and IGF-1/IGFBP-3 molar ratio on mammographic density: a cross-sectional study

  • M.L. Meggiorini1,*,
  • V. Cipolla2
  • G. Borgoni1
  • I. Nofroni3
  • A. Pala1
  • C. de Felice2

1Department of Obstetric and Gynaecological Sciences and Urological Sciences, , Rome, Italy

2Department of Radiological Sciences, Rome, Italy

3Department of Experimental Medicine, “Sapienza” University of Rome, Rome, Italy

DOI: 10.12892/ejgo20120174 Vol.33,Issue 1,January 2012 pp.74-78

Published: 10 January 2012

*Corresponding Author(s): M.L. Meggiorini E-mail:


The purpose of this study was to examine the possible effects of IGF-1, IGFBP-3 and IGF-1/IGFBP-3 molar ratio on manunographic density and assess whether this relationship was similar in subgroups of pre- and postmenopausal women. A group of 341 Italian women of childbearing age or naturally postmenopausal who had performed mammographic examination at the section of radiology of our department a maximum three months prior to recruitment were enrolled. A blood sample was drawn for determination of IGF-1, IGFBP-3 levels and IGF-1/IGFBP-3 molar ratio was calculated. On the basis of recent mammograms the women were divided into two groups: dense breast (DB) and non-dense breast (NDB). To assess the association between mammographic density and IGF-1, IGFBP-3 and Molar ratio Student's t-test was employed before and after stratified by menopausal status. The analysis of the relationship between mammographic density and plasma levels of IGF-1, IGFBP-3 and IGF-1/IGFBP-3 molar ratio showed that IGF-1 levels and molar ratio varied in the two groups resulting in higher mean values in the DB group whereas IGFBP-3 showed similar values in both groups (DB and NDB). After stratification of the study population by menopausal status, no association was found. Our study provides strong evidence of a crude association between breast density, and plasma levels of IGF-1 and molar ratio. IGF-1 and molar ratio might increase mammographic density and thus the risk of developing breast cancer.


IGF-1; IGFBP-3; IGF-1/IGFBP-3; Molar ratio; Mammographic density; Breast cancer risk

Cite and Share

M.L. Meggiorini,V. Cipolla,G. Borgoni,I. Nofroni,A. Pala,C. de Felice. Possible effects of insulin-like growth factor-I, IGF-binding protein-3 and IGF-1/IGFBP-3 molar ratio on mammographic density: a cross-sectional study. European Journal of Gynaecological Oncology. 2012. 33(1);74-78.


[1] Wood T.L., Yee D.: “Introduction: IGFs and IGFBPs in the normal mammary gland and in breast cancer”. J. Mammary Gland. Biol. Neoplasia, 2000, 5, 1.

[2] Sachdev D., Yee D.: “The IGF system and breast cancer”. Endocr. Relat. Cancer, 2001, 8, 197.

[3] Mikami K., Ozasa K., Nakao M., Miki T., Hayashi K., Watanabe Y. et al., JACC Study Group: “Prostate cancer risk in relation to insulin-like growth factor (IGF)-I and IGF-binding protein-3: A nested case-control study in large scale cohort study in Japan”. Asian Pac. J. Cancer Prev., 2009, 10 (suppl.), 57.

[4] Bostedt K.T., Schmid C., Ghirlanda-Keller C., Olie R., Winterhalter KH, Zapf J.: “Insulin-like growth factor (IGF) I down-regulates type 1 IGF receptor (IGF 1R) and reduces the IGF I response in A549 non-small-cell lung cancer and Saos-2/B-10 osteoblastic osteosarcoma cells”. Exp. Cell Res., 2001, 271, 368.

[5] Li B.D., Khosravi M.J., Berkel H.J., Diamandi A., Dayton M.A., Smith M.H.: “Free insulin-like growth factor-I and breast cancer risk”. Int. J. Cancer, 2001, 91, 736.

[6] Pollak M.N., Schernhammer E.S., Hankinson S.E.: “Insulin-like growth factors and neoplasia”. Nat. Rev. Cancer, 2004, 4, 505.

[7] O’Han M.K., Baxter R.C., Schedlich L.J.: “Effects of endogenous insulin-like growth factor binding protein-3 on cell cycle regulation in breast cancer cells”. Growth Factors, 2009, 12, 1.

[8] Helle S.I.: “The insulin-like growth factor system in advanced breast cancer”. Best. Pract. Clin. Endocrinol. Metab., 2004, 18, 67.

[9] Jerome L., Shiry L., Leyland-Jones B.: “Anti-insulin-like growth factor strategies in breast cancer”. Semin. Oncol., 2004, 31, 54.

[10] Firth S.M., Baxter R.C.: “Cellular actions of the insulin-like growth factor binding proteins”. Endocr. Rev., 2002, 23, 824.

[11] Siwanowicz I., Popowicz G.M., Wisniewska M., Huber R., Kuenkele K.P., Lang K. et al.: “Structural basis for the regulation of insulin-like growth factors by IGF binding proteins”. Structure, 2005, 13, 155.

[12] Endogenous Hormones and Breast Cancer Collaborative Group, Key T.J., Appleby P.N., Reeves G.K., Roddam A.W.: “Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies”. Lancet Oncol., 2010, 11, 530.

[13] Baglietto L., Dallas R. English, Hopper J.L., Morris H.A., Tilley W.D., Giles G.G.: “Circulating insulin-like growth factor-I and binding protein-3 and the risk of breast cancer”. Cancer Epidemiol. Biomarkers Prev., 2007, 16, 763.

[14] Taverne C.W., Verheus M., McKay J.D., Kaaks R., Canzian F., Grobbee D.E. et al.: “Common genetic variation of insulin-like growth factor-binding protein 1 (IGFBP-1), IGFBP-3, and acid labile subunit in relation to serum IGF -I levels and mammographic density”. Breast Cancer Res. Treat., 2010, 123, 843.

[15] Shi R., Yu H., McLarty J., Glass J.: “IGF-I and breast cancer: a meta-analysis”. Int. J. Cancer, 2004, 111, 418.

[16] Mathews L., Schneider S.S.: “Insulin-like growth factor-I inhibits growth regulatory responses engaged by estrogen and progesterone in the mouse mammary gland”. Eur. J. Cancer Prev., 2008, 17, 297.

[17] Johansson H., Gandini S., Bonanni B., Mariette F., Guerrieri-Gonzaga A., Serrano D. et al.: “Relationships between circulating hormone levels, mammographic percent density and breast cancer risk factors in postmenopausal women”. Breast Cancer Res. Treat., 2008, 108, 57.

[18] Schernhammer E.S., Holly J.M., Pollak M.N., Hankinson S.: “Circulating levels of insulin-like growth Factors, their Binding Proteins, and breast cancer risk”. Cancer Epidemiol Biomarkers Prev., 2005, 14.

[19] Schernhammer E.S., Holly J.M., Hunter D.J., Pollak M.N., Hankinson S.E.: “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”. Endocrine-related Cancer, 2006, 13, 583.

[20] Harvey J.A., Bovbjerg V.E.: “Quantitative assessment of mammographic breast density: relationship with breast cancer risk”. Radiology, 2004, 230, 29.

[21] Boyd N.F., Guo H., Martin L.J., Sun L., Stone J., Fishell E. et al.: “Mammographic density and the risk and detection of breast cancer”. N. Engl. J. Med., 2007, 356, 227.

[22] Vachon M.C., van Gils C.H., Sellers T.A., Ghosh K., Pruthi S., Brandt K.R., Pankratz V.S.: “Mammographic density, breast cancer risk and risk prediction”. Breast Cancer Res., 2007, 9, 217.

[23] Boyd N.F., Rommens J.M., Vogt K., Lee V., Hopper J.L., Yaffe M.J., Paterson A.D.: “Mammographic breast density as an intermediate phenotype for breast cancer”. Lancet Oncol., 2005, 6, 798.

[24] McCormack V.A., dos Santos Silva I.: “Breast density and parenchymal patterns as markers of breast cancer risk: a metaanalysis”. Cancer Epidemiol. Biomarkers Prev. 2006, 15, 1159.

[25] Byrne C., Colditz G.A., Willett W.C., Speizer F.E., Pollk M., Hankinson S.E.: “Plasma insulin growth factor (IGF-I), IGF -binding protein 3, and mammographic density”. Cancer Res., 2000, 60, 3744.

[26] Diorio C., Pollak M., Byrne C., Mâsse B., Herbert-Croteau N., Yaffe M. et al.: “Insulin-like growth factor-1, IGF-binding protein-3, and mammographic breast density”. Cancer Epidemiol. Biomarkers Prev., 2005, 14, 1065.

[27] Maskarinec G., Williams A.E., Kaas R.: “A cross-sectional investigation of breast density and insulin-like growth factor I”. Int. J. Cancer, 2003, 107, 991.

[28] dos Santos Silva I., Johnson N., De Stavola B., Torres-Mejìa G., Fletcher O., Allen N.E. et al.: “The insulin-like growth factor system and mammographic features in premenopausal and postmenopausal women”. Cancer Epidemiol. Biomarkers Prev., 2006, 15, 449.

[29] Bremnes Y., Ursin G., Bjurstam N., Rinaldi S., Kaaks R., Gram I.T.: “Endogenous sex hormones, prolactin and mammographic density in postmenopausal Norwegian women. International journal of cancer”. Int. J. Cancer, 2007, 121, 2506.

[30] Bremnes Y., Ursin G., Bjurstam N., Rinaldi S., Kaaks R., Gram I.T.: “Insulin-like growth factor and mammographic density in postmenopausal Norwegian women”. Cancer Epidemiol. Biomarkers Prev., 2007, 16, 57.

[31] Aiello E.J., Tworoger S.S., Yasui Y., Stanczyk F.Z., Potter J., Ulrich C.M. et al.: “Associations among circulating sex hormones, insulin-like growth factor, lipids, and mammographic density in postmenopausal women”. Cancer Epidemiol. Biomarkers Prev., 2005, 14, 1411.

[32] Liberman L., Menell J.H.: “Breast imaging reporting and data system (BIRADS)”. Radiol. Clin. North Am., 2002, 40, 409.

[33] Balleyguier C., Ayadi S., Nguyen K.V., Vanel D., Dromain C., Sigal R.: “BIRADSTM classification in mammography”. EJR, 2007, 61, 192.

[34] Yu H., Jin F., Shu X.O., Li B.D., Dai Q., Cheng J.R. et al.: “Insulin-like growth factors and breast cancer risk in Chinese women”. Cancer Epidemiol. Biomarkers Prev., 2002, 11, 705.

[35] Maskarinec G., Takata Y., Chen Z., Gram I.T., Nagata C., Pagano I. et al.: “IGF-I and mammographic density in four geographic locations: a pooled analysis”. Int. J. Cancer, 2007, 121, 1786.

[36] Campagnoli C., Abbà C., Ambroggio S., Peris C.: “Differential effects of progestins on the circulating IGF-I system”. Maturitas, 2003, 10, 46 (suppl. 1), S39.

[37] Chia V.M., Newcomb P.A., White E., Zheng Y., Potter J.D., Lampe J.W.: “Reproducibility of serum leptin, insulin-like growth factor-I, and insulin-like growth factor-binding protein-3 measurements”. Horm. Res., 2008, 69, 295.

[38] Borofsky N.D., Vogelman J.H., Krajcik R.A., Orentreich N.: “Utility of insulin-like growth factor-1 as a biomarker in epidemiological studies”. Clin. Chem., 2002, 48, 2248.

[39] Milani D., Carmichael J.D., Welkowitz J., Ferris S., Reitz R.E., Danoff A., Kleinberg D.L.: “Variability and reliability of single serum IGF -measurements: impact on determining predictability of risk ratios in disease development”. J. Clin. Endocrinol. Metab., 2004, 89, 2271.

[40] Dabrosin C.: “Increase of free insulin-like growth factor-1 in normal human breast in vivo late in menstrual cycle”. Breast Cancer Res. Treat., 2003, 80, 193.

[41] Friedrich N., Krebs A., Nauck M., Wallaschofski H.: “Age- and gender-specific reference ranges for serum insulin-like growth factor I (IGF-I) and IGF-binding protein-3 concentrations on the Immulite 2500: results of the Study of Health in Pomerania (SHIP)”. Clin. Chem. Lab. Med., 2010, 48, 115.

[42] Yaffe M.J.: “Mammographic density. Measurement of mammographic density”. Breast Cancer Res., 2008, 10, 209.

[43] Martin L.J., Melnichouk O., Guo H., Chiarelli A.M., Hislop T.G., Yaffe M.J. et al.: “Family history, mammographic density, and risk of breast cancer”. Cancer Epidemiol. Biomarkers Prev., 2010, 19, 456.

[44] Boyd N.F., Lockwood G.A., Martin L.J., Byng J.W., Yaffe M.J., Tritchler D.L.: “Mammographic density as a marker of susceptibility to breast cancer: a hypothesis”. IARC Sci. Publ., 2001, 154, 163.

[45] Diorio C., Brisson J., Bérubé S., Pollak M.: “Genetic polymorphisms involved in insulin-like growth factor (IGF) pathway in relation to mammographic breast density and IGF levels”. Cancer Epidemiol. Biomarkers Prev., 2008, 17, 880.

[46] Diorio C., Brisson J., Bérubé S., Pollak M.: “Intact and total insulin-like growth factor-binding protein-3 (IGFBP-3) levels in relation to breast cancer risk factors: a cross-sectional study”. Breast Cancer Res., 2008, 10, R42.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time