Epidermal growth factor in breast cyst fluid: relationship with intracystic cation and androgen conjugate content

In recent years, several studies focused on the biochemical analysis of breast cyst fluid composition. It has been shown that breast cysts lined by apocrine epithelium contain higher levels of potassium and dehydroepiandrosterone-sulphate as compared to cysts lined by flattened cells, and that women with apocrine cysts are more likely to develop breast cancer. In the present study, we measured the intracystic levels of sodium (Na+), potassium (K+), dehydroepiandrosterone-sulphate (DHEA-S), and epidermal growth factor (EGF), a factor which could play a role in the autocrine or paracrine control of breast cancer cell growth as recently proposed by some investigators. Breast cyst fluids obtained by fine-needle aspiration from 86 women with gross cystic breast disease were assayed. On the basis of the relative intracystic concentrations of Na+ and K+ two main classes of cysts were defined. An arbitrary cut-off value of 3 for the Na+/K+ ratio seemed adequate to separate these two types of cysts. An inverse relationship was found between the Na+/K+ ratio and DHEA-S concentration, median levels of the androgen conjugate being 3615 micrograms/dl in Na+/K+ less than 3 cysts and 480 micrograms/dl in Na+/K+ greater than 3 cysts (P less than 0.001). EGF levels were found to be significantly higher in Na+/K+ less than 3 cysts as compared to Na+/K+ greater than 3 cysts: 103.26 ng/ml versus 57.22 ng/ml, respectively (P less than 0.001). EGF appeared inversely correlated with total protein concentration in the Na+/K+ greater than 3 cysts, while in the Na+/K+ less than 3 cysts high EGF levels were observed independently of total protein content. In addition, a direct correlation was found between EGF and DHEA-S concentrations. On the basis of these results, the hypothesis can be made that EGF, which is measurable in all breast fluids tested and is nearly undetectable in plasma, is actually produced by the epithelium lining the cyst wall, particularly as far as the Na+/K+ less than 3 cysts are concerned. In view of our results this type of cyst, which has been shown to be lined by apocrine epithelium, appears to be characterized by high DHEA-S and EGF levels. It is suggested that the latter finding could provide a clue for understanding the increased risk of subsequent breast cancer in women bearing apocrine cysts.