Plasma insulin-like growth factor (IGF) I, IGF-binding protein 3, and mammographic density.
Insulin-like growth factors (IGFs) and insulin-like growth factor-binding proteins (IGFBPs) play a role in the normal development of breast tissue and possibly in the etiology of breast cancer. Breast density is one of the strongest predictors of breast cancer. In a cross-sectional analysis within the Nurses' Health Study, we compared the associations of plasma levels of endogenous IGF-I and IGFBP-3 with breast density in 65 premenopausal and 192 postmenopausal women. The digitized film screen mammograms were evaluated by the computer-assisted Toronto method, in which visually selected gray-scale cut points are used to assess breast density. Generalized linear models and Spearman's partial correlation coefficients described the associations between breast density and IGF-I, IGFBP-3, and the IGF-I:IGFBP-3 ratio. Premenopausal breast density was positively correlated with IGF-I and inversely correlated with IGFBP-3; the association was strongest for the IGF-I:IGFBP-3 ratio and breast density (r = 0.39; P = 0.004). In contrast, the correlation between breast density and the IGF-I:IGFBP-3 ratio among postmenopausal women was -0.02 (P = 0.83). The associations of IGF-I:IGFBP-3 ratio with breast density differed significantly between premenopausal and postmenopausal women (P = 0.01). Mammographic density is positively associated with plasma IGF-I levels and inversely associated with plasma IGFBP-3 levels among premenopausal women, but not among postmenopausal women. These results are consistent with previous studies that showed a positive association between a higher IGF-I:IGFBP-3 ratio and subsequent risk of breast cancer only among premenopausal women. The findings raise the possibility that premenopausal levels of IGF-I and IGFBP-3 could be in the etiological pathway that relates higher breast density with increased breast cancer risk.
Byrne
C
C
Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Colditz
G A
GA
Willett
W C
WC
Speizer
F E
FE
Pollak
M
M
Hankinson
S E
SE
D000368:Aged; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008327:Mammography; D008875:Middle Aged; D010949:Plasma / Q000378:metabolism; D017698:Postmenopause; D017697:Premenopause; D012307:Risk Factors
D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I