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Influence of Insulin-like Growth Factors on the Strength of the Relation of Vitamin D and Calcium Intakes to Mammographic Breast Density

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, Laval University; and ⁴ Clinique Radiologique Audet, Québec, Canada; ⁵ Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia; ⁶ Fred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, Washington; ⁷ Institut national de santé publique du Québec et Centre de recherche, Hôpital Charles LeMoyne, Greenfield, Canada; ⁸ Sunnybrook & Women's College Health Sciences Centre, University of Toronto, Toronto, Canada; and ⁹ Department of Medicine and Oncology, Cancer Prevention Research Unit, Lady Davis Institute of the Jewish General Hospital and McGill University, Montréal, 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, Québec, Québec, Canada G1S 4L8. Phone: 418-682-7392; Fax: 418-682-7949; E-mail: jacques.brisson{at}uresp.ulaval.ca.

Diets with higher vitamin D and calcium contents were found associated with lower mammographic breast density and breast cancer risk in premenopausal women. Because laboratory studies suggest that the actions of vitamin D, calcium, insulin-like growth factor (IGF)-I, and IGF-binding protein-3 (IGFBP-3) on human breast cancer cells are interrelated, we examined whether IGF-I and IGFBP-3 levels could affect the strength of the association of vitamin D and calcium intakes with breast density. Among 771 premenopausal women, breast density was measured by a computer-assisted method, vitamin D and calcium intakes by a food frequency questionnaire, and levels of plasma IGF-I and IGFBP-3 by ELISA methods. Multivariate linear regression models were used to examine the associations and the interactions. The negative associations of vitamin D or calcium intakes with breast density were stronger among women with IGF-I levels above the median (ß = –2.8, P = 0.002 and ß = –2.5, P = 0.002, respectively) compared with those with IGF-I levels below or equal to the median (ß = –0.8, P = 0.38 and ß = –1.1, P = 0.21; P_interaction = 0.09 and 0.16, respectively). Similar results were observed within levels of IGFBP-3 (P_interaction = 0.06 and 0.03, respectively). This is the first study to report that the negative relation of vitamin D and calcium intakes with breast density may be seen primarily among women with high IGF-I or high IGFBP-3 levels. Our findings suggest that the IGF axis should be taken into account when the effects of vitamin D and calcium on breast density (and perhaps breast cancer risk) are examined at least among premenopausal women. (Cancer Res 2006; 66(1): 588-97)

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