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Increased breast cancer risks have been reported among women with gross cystic breast disease (GCBD), although the mechanism for this increase remains unexplained. Relationships between GCBD characteristics, breast cancer risk factors, and the biochemical composition and growth properties of 142 breast cyst fluid (BCF) samples were studied among 93 women with GCBD. Concentrations of melatonin, estrogen (17-beta-estradiol), dehydroepiandrosterone-sulfate (DHEA-S), epidermal growth factor (EGF), transforming growth factor beta (TGF-B1 and TGF-B2), sodium (Na), and potassium (K) were quantified in BCF samples, and human breast cancer cells (MCF-7) were treated with BCF in vitro. Patients were grouped according to BCF Na:K ratios previously linked with increased breast cancer risks (Na:K 3, Type 2) and mixed cyst groups. Women with larger and more frequently occurring cysts had higher BCF estrogen and DHEA-S, and lower TGF-B1 levels. Women with Type 1 cysts had elevated BCF melatonin, estrogen, DHEA-S, and EGF, and lower concentrations of TGF-B2 compared to women with Type 2 cysts. BCF generally inhibited cell growth relative to serum-treated controls, consistent with previous studies. Melatonin and estrogen in BCF independently predicted growth inhibition and stimulation, respectively. Biological monitoring of BCF may help identify women with GCBD at greatest risk for breast cancer development.

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