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1 Unité de recherche en santé des populations and 2 Centre des maladies du sein Deschênes-Fabia, Centre hospitalier affilié universitaire de Québec; 3 Department of Social and Preventive Medicine and 4 Laboratoire d'anatomo-pathologie, département de biologie médicale, Laval University; and 5 Clinique Radiologique Audet, Quebec, Quebec, Canada; 6 Departments of Medicine and Oncology, Cancer Prevention Research Unit, Lady Davis Institute of the Jewish General Hospital and McGill University, Montreal, Quebec, Canada; 7 Lombardi Cancer Center, Georgetown University, Washington, District of Columbia; 8 Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; 9 Institut national de santé publique du Québec et Centre de recherche, Hôpital Charles LeMoyne, Greenfield, Quebec, Canada; and 10 Sunnybrook & Women's College Health Sciences Centre, University of Toronto, Toronto, Canada
Requests for reprints: Jacques Brisson, Unité de recherche en santé des populations, Centre hospitalier affilié universitaire de Québec, Hôpital Saint-Sacrement, 1050 Chemin Sainte-Foy, Quebec, Quebec, Canada G1S 4L8. Phone: 418-682-7392; Fax: 418-682-7949. E-mail: jacques.brisson{at}uresp.ulaval.ca
Some studies have suggested that insulin-like growth factor (IGF) pathway is related to premenopausal breast density, one of the strongest known breast cancer risk factors. This study was designed specifically to test the hypothesis that higher levels of IGF-I and lower levels of IGF-binding protein (IGFBP)-3 are associated with high mammographic breast density among premenopausal but not among postmenopausal women. A total of 783 premenopausal and 791 postmenopausal healthy women were recruited during screening mammography examinations. Blood samples were collected at the time of mammography, and plasma IGF-I and IGFBP-3 levels were measured by ELISA. Mammographic breast density was estimated using a computer-assisted method. Spearman's partial correlation coefficients (rs) were used to evaluate the associations. Adjusted mean breast density was assessed by joint levels of IGF-I and IGFBP-3 using generalized linear models. Among premenopausal women, high levels of IGF-I and low levels of IGFBP-3 were independently correlated with high breast density (rs = 0.083; P = 0.021 and rs = –0.124; P = 0.0005, respectively). Correlation of IGF-I with breast density was stronger among women in the lowest tertile of IGFBP-3 than among those in the highest tertile of IGFBP-3 (rs = 0.138; P = 0.027 and rs = –0.039; P = 0.530, respectively). In contrast, the correlation of IGFBP-3 with breast density was stronger among women in the highest tertile of IGF-I than among those in the lowest tertile of IGF-I (rs = –0.150; P = 0.016 and rs = –0.008; P = 0.904, respectively). Women in the combined top tertile of IGF-I and bottom tertile of IGFBP-3 had higher mean breast density than those in the combined bottom tertile of IGF-I and top tertile of IGFBP-3 (53.8% versus 40.9%; P = 0.014). No significant association was observed among postmenopausal women. Our findings confirm that IGF-I and IGFBP-3 are associated with breast density among premenopausal women. They provide additional support for the idea that, among premenopausal women, these growth factors may affect breast cancer risk, at least in part, through their influence on breast tissue morphology as reflected on mammogram.
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C. M. Vachon, K. R. Brandt, K. Ghosh, C. G. Scott, S. D. Maloney, M. J. Carston, V. S. Pankratz, and T. A. Sellers Mammographic Breast Density as a General Marker of Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., January 1, 2007; 16(1): 43 - 49. [Abstract] [Full Text] [PDF]
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Y. Bremnes, G. Ursin, N. Bjurstam, S. Rinaldi, R. Kaaks, and I. T. Gram Insulin-like Growth Factor and Mammographic Density in Postmenopausal Norwegian Women Cancer Epidemiol. Biomarkers Prev., January 1, 2007; 16(1): 57 - 62. [Abstract] [Full Text] [PDF]
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C. D. Tran, C. Diorio, S. Berube, M. Pollak, and J. Brisson Relation of insulin-like growth factor (IGF) I and IGF-binding protein 3 concentrations with intakes of fruit, vegetables, and antioxidants Am. J. Clinical Nutrition, December 1, 2006; 84(6): 1518 - 1526. [Abstract] [Full Text] [PDF]
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N. F. Boyd, L. J. Martin, L. Sun, H. Guo, A. Chiarelli, G. Hislop, M. Yaffe, and S. Minkin Body Size, Mammographic Density, and Breast Cancer Risk. Cancer Epidemiol. Biomarkers Prev., November 1, 2006; 15(11): 2086 - 2092. [Abstract] [Full Text] [PDF]
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 C. J. Fabian and B. F. Kimler Mammographic Density: Use in Risk Assessment and as a Biomarker in Prevention Trials J. Nutr., October 1, 2006; 136(10): 2705S - 2708S. [Full Text] [PDF]
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 C. M. Blakely, A. J. Stoddard, G. K. Belka, K. D. Dugan, K. L. Notarfrancesco, S. E. Moody, C. M. D'Cruz, and L. A. Chodosh Hormone-Induced Protection against Mammary Tumorigenesis Is Conserved in Multiple Rat Strains and Identifies a Core Gene Expression Signature Induced by Pregnancy. Cancer Res., June 15, 2006; 66(12): 6421 - 6431. [Abstract] [Full Text] [PDF]
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I. dos Santos Silva, N. Johnson, B. De Stavola, G. Torres-Mejia, O. Fletcher, D. S. Allen, N. E. Allen, T. J. Key, I. S. Fentiman, J. M.P. Holly, et al. The insulin-like growth factor system and mammographic features in premenopausal and postmenopausal women. Cancer Epidemiol. Biomarkers Prev., March 1, 2006; 15(3): 449 - 455. [Abstract] [Full Text] [PDF]
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C. Diorio, S. Berube, C. Byrne, B. Masse, N. Hebert-Croteau, M. Yaffe, G. Cote, M. Pollak, and J. Brisson Influence of Insulin-like Growth Factors on the Strength of the Relation of Vitamin D and Calcium Intakes to Mammographic Breast Density Cancer Res., January 1, 2006; 66(1): 588 - 597. [Abstract] [Full Text] [PDF]
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R. Kaaks, C. Diorio, and J. Brisson Insulin-Like Growth Factor-I and Mammographic Breast Density Cancer Epidemiol. Biomarkers Prev., December 1, 2005; 14(12): 3019 - 3019. [Full Text] [PDF]
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C. Diorio, M. Pollak, C. Byrne, B. Masse, N. Hebert-Croteau, M. Yaffe, G. Cote, S. Berube, and J. Brisson Levels of C-Peptide and Mammographic Breast Density Cancer Epidemiol. Biomarkers Prev., November 1, 2005; 14(11): 2661 - 2664. [Abstract] [Full Text] [PDF]
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