Premenopausal levels of circulating insulin-like growth factor I and the risk of postmenopausal breast cancer

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Abstract
Increased levels of insulin‐like growth factor I (IGF‐I) may directly stimulate breast cell proliferation and promote growth and survival of transformed cells. Higher levels of IGF‐I have been associated with increased risk of premenopausal breast cancer but not postmenopausal breast cancer. We investigated whether circulating levels of IGF‐I prior to menopause are associated with breast cancer diagnosed after menopause in a population‐based nested case‐control study. Female cohort participants were enrolled in 1974 (n = 15,192) and 1989 (n = 18,724) and blood was drawn. Cases were women diagnosed with primary breast cancer at ages ≥50, of whom 152 were premenopausal at blood draw. One control was matched to each case on cohort participation, age, ethnic group, menopausal status and date of blood draw. Levels of IGF‐I and IGF binding protein 3 (IGFBP‐3) were measured using enzyme‐linked immunoabsorbant assays assays. The association between IGF‐I and breast cancer was determined using conditional logistic regression, adjusting for IGFBP‐3. IGF‐I levels decreased with age (p = 0.0001). Prior to age‐stratification, IGF‐I levels neither measured before nor after menopause were associated with postmenopausal breast cancer. After age‐stratification, associations were suggested in the youngest premenopausal age group (upper vs. lowest third: odds ratio (OR) = 5.31, 95% confidence intervals (CI) = 0.85–33.13; p trend = 0.06) and oldest postmenopausal age group (upper vs. lowest third: OR = 3.41, 95% CI = 0.66–17.71; p trend = 0.13). The association between circulating levels of IGF‐I and postmenopausal breast cancer risk may be modified by age. Increased levels of circulating IGF‐I may be of particular interest in the younger premenopausal women and older postmenopausal women. Age‐stratification should be undertaken in larger investigations of IGF‐I levels as predictors of postmenopausal breast cancer.

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