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Insulin-like Growth Factor I in Pregnancy and Maternal Risk of Breast Cancer

Departments of ¹ Obstetrics and Gynecology and ² Environmental Medicine, New York University School of Medicine, New York, New York; and Departments of ³ Public Health and Clinical Medicine/Nutritional Research, ⁴ Medical Biosciences, ⁵ Clinical Sciences, ⁶ Oncology, ⁷ Radiation Sciences, and ⁸ Clinical Microbiology, University of Umeå, Umeå, Sweden

Requests for reprints: Annekatrin Lukanova, Division of Epidemiology, Department of Obstetrics and Gynecology, New York University School of Medicine, 550 First Avenue, NBV 9E2, New York, NY 10016. Phone: 212-263-0486; Fax: 212-263-8887. E-mail: lukana01{at}med.nyu.edu

Background: The role of insulin-like growth factor (IGF)-I in breast cancer remains controversial, despite numerous reports on the association of the hormone with breast cancer or high-risk mammographic densities. We hypothesized that exposure to elevated IGF-I during early pregnancy, a period characterized by intense cell proliferation in the breasts and in the presence of high concentrations of sex steroids, will be associated with increased maternal risk to develop a breast malignancy.

Methods: The Northern Sweden Maternity Cohort is an ongoing prospective study, collecting blood samples from first-trimester-pregnant women since 1975 as part of screening for infectious diseases. A case-control study (212 cases and 369 controls) was nested among Northern Sweden Maternity Cohort members who delivered singleton babies. RIA was used to measure IGF-I and IGF-II levels. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI).

Results: Breast cancer risk increased with increasing IGF-I (top tertile OR, 1.7; 95% CI, 1.1-2.7). The association was stronger among the primiparous (OR, 2.2; 95% CI, 1.1-4.4) than in the nonprimiparous women (OR, 1.4; 95% CI, 0.7-2.8). Upper-tertile risks seemed to decrease within the <28-, 28 to 33, and >33-year groups of age at sampling, from 2.5 (0.9-7.6) to 2.1 (0.9-5.0) and 1.2 (0.5-2.5), respectively. There was no association of breast cancer with first-trimester-pregnancy IGF-II.

Conclusions: The study offers further evidence that IGF-I is important in breast cancer. Our findings suggest that the adverse effect of IGF-I on the breast may be stronger before the remodeling of the gland induced by a first pregnancy. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2489–93)