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Premenopausal Insulin-Like Growth Factor-I Serum Levels and Changes in Breast Density over Menopause

¹ Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands and ² Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany

Requests for reprints: Carla H. van Gils, Julius Center for Health Sciences and Primary Care, University Medical Center, Room Str 6.131, P. O. Box 85500, Utrecht 3508 GA, the Netherlands. E-mail: C.vanGils{at}umcutrecht.nl

Background: A high proportion of glandular and stromal tissue in the breast (percentage breast density) is a strong risk factor for breast cancer development. Insulin-like growth factor-I (IGF-I) is hypothesized to influence breast cancer risk by increasing breast density.

Objectives: We studied the relation between premenopausal circulating IGF-I levels and premenopausal and postmenopausal, absolute nondense and dense area, and percentage breast density as well as changes in these measures over menopause.

Design and Methods: Mammograms and blood samples of 684 premenopausal participants of the Prospect-European Prospective Investigation into Cancer and Nutrition cohort were collected at baseline. A second mammogram of these women was collected after they became postmenopausal. Premenopausal IGF-I levels were measured in serum. Premenopausal and postmenopausal breast measures were assessed using a computer-assisted method. Mean values of breast measures were calculated for quartiles of serum IGF-I using linear regression analysis.

Results: Women with higher premenopausal IGF-I levels showed a slightly smaller decrease in dense area over menopause (–12.2 cm² in the highest versus –12.9 cm² in the lowest quartile; P trend = 0.58) and, at the same time, a smaller increase in the nondense (fat) area (P trend = 0.09). Due to the changes over menopause, high premenopausal IGF-I serum levels were associated with lower nondense area (P trend = 0.05), somewhat higher dense area (P trend = 0.66), and consequently higher percentage breast density (P trend = 0.02) after menopause.

Conclusion and Discussion: Women with higher premenopausal IGF-I levels have a smaller increase in nondense area and also a slightly smaller decrease in absolute dense area during menopause, resulting in higher breast density after menopause. (Cancer Epidemiol Biomarkers Prev 2007;16(3):451–7)