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Purpose: Variations during breast tissue development can influence later breast cancer risk. In particular, prolonged nulliparity increases risk. The authors used optical spectroscopy to compare breast tissue in 115 nulliparous women aged 31-40 (group 2) to 140 nulliparous women aged 18-21 (group 1), and also to 36 parous women aged 31-40 (group 3), and to evaluate the relationship between IGF-1 and optical breast tissue properties. IGF-1 has been linked in particular to premenopausal breast cancer., Methods: The authors measured the transmission spectra from 625 to 1050 nm wavelengths in each breast and determined regions of interindividual variation using principal components analysis. Spectral differences represent variation in lipid, water, oxyhemoglobin, deoxyhemoglobin, and collagen content. Group differences and the relationship with IGF-1 were estimated by linear regression after adjustment for multiple factors including height, weight, ethnicity, hormonal contraceptive use, and days since last menstrual period., Results: Principal component 3 scores were more negative in the older nulliparous women compared to either younger nulliparous women or to parous women of the same age (beta = -0.16, p = 0.008 for group 2 vs group 1 and beta = 0.51, p = 0.03 for group 3 vs group 2). These differences appear to indicate increased deoxyhemoglobin relative to oxyhemoglobin content in the tissue of the older, nulliparous premenopausal women compared to the other groups, which may be an indicator of proportionally increased proliferative tissue. Principal component 4 also differed between older and younger nulliparous women (beta = 0.08, p = 0.02 for group 2 vs. group 1) and was negatively associated with IGF-1 in younger women (beta = -0.0004, p = 0.03) and positively associated with IGF-1 in older women (beta = 0.001, p = 0.004)., Conclusions: Optical spectroscopy may be useful to identify breast tissue at increased risk of cancer development and track changes over time, particularly in young women where exposure to radiation is of particular concern. Additional work is needed to confirm the observed breast tissue differences and to determine the specific tissue chromophore changes with age and parity.