estrone-sulfate and Breast-Diseases

The ability of breast tumors to synthesize sex steroid hormones is well recognized and their local production is thought to play a role in breast cancer development and growth. The aim of this study was to estimate local intra-tumoral and circulating levels of Estrone (E1), Estrone Sulfate (E1S), Estradiol (E2), Estriol (E3), and Testosterone (T) in 33 pre- and postmenopausal women with primary breast cancer in comparison to 12 pre- and postmenopausal women with benign breast tumors. The mean levels of the studied sex hormones were higher in serum and tumor tissue of breast cancer women than those with benign breast tumors apart from Testosterone which showed a significant decrease in pre- and postmenopausal women with breast cancer (P<0.001for follicular phase, P<0.05 for luteal phase, and P<0.005 for postmenopausal). The levels of the five hormones were significantly higher intra-tumoral than in serum of both benign and malignant breast tumor women with E1S as the predominant estrogen. There was only a positive significant correlation between serum and tumor tissue levels of E1 (rs=0.52, P<0.05 for follicular; rs=0.63, P<0.05 for luteal and rs=0.58, P<0.05 for postmenopausal) and a significant correlation between serum and tumor tissue of T (rs=0.64, P<0.05 for follicular; rs=-0.51, P<0.05 for luteal and rs=-0.81, P<0.04 for postmenopausal).

Topics: Adult; Aged; Biomarkers; Breast Diseases; Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Estradiol; Estriol; Estrone; Female; Fibroadenoma; Follicular Phase; Gonadal Steroid Hormones; Humans; Luteal Phase; Middle Aged; Postmenopause; Premenopause; Testosterone

Estriol-3-sulfate (E3S) is present in human breast cyst fluid (BCF) in median levels of 8.7-10.4 nmol/L, yet is barely detectable in the serum (less than 0.034 nmol/L). The source of this huge concentration of E3S is unknown. It may accumulate from blood by active transport or be synthesized and concentrated within the cyst. Since estrone sulfate (E1S) and its possible precursor, dehydroepiandrosterone sulfate (DHEAS) are elevated in BCF, E3S may originate via 16 alpha-hydroxylation of E1S. The present study examined the correlations between the levels of DHEAS and E1S with those of E3S in BCF. The sodium and potassium ions were also quantified and related to the steroid concentrations. By linear regression analysis of log-normalized data there was a highly significant correlation between the concentrations of E1S and E3S (n = 355, r = 0.690, P less than 0.001) and between DHEAS and E3S (n = 361, r = 0.577, P less than 0.001). The BCF were classified according to their K/Na ion ratios: type 1, greater than 1.0, type II, less than 0.25, and type III, 0.25-1.0. By Student's t test, the concentrations of E3S differed between each BCF Type (P less than 0.002). This was also true for E1S and DHEAS. Type 1 cysts were associated with the highest estrogen sulfate levels and type II with the lowest levels. The possible physiological importance of this observation resides in reports that the BCF type expressing the highest steroid concentrations has been related to an aporcine-like epithelial lining of the cyst wall and a somewhat higher risk for developing breast cancer. The results suggest that E3S in BCF may originate from E1S, but alternate mechanisms are not precluded.

Topics: Aryl Hydrocarbon Hydroxylases; Body Fluids; Breast Diseases; Cysts; Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP2C9; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estriol; Estrone; Humans; Osmolar Concentration; Potassium; Regression Analysis; Sodium; Steroid 16-alpha-Hydroxylase

To investigate the possibility of increased tissue exposure to estrogen in breast cancer patients, plasma levels of estrogens and the percentage of unbound estradiol were measured in postmenopausal women with benign or malignant breast disease and compared with levels in normal postmenopausal women. The percentage of unbound estradiol in breast cancer patients [1.85 +/- 0.35% (S.D.)] was significantly higher (p less than 0.001) than in normal postmenopausal women [1.52 +/- 0.33%] and was still significantly higher when patients were matched with control subjects for weight (p less than 0.001) or ideal body weight (p less than 0.001). The binding capacity of sex hormone binding globulin was similar in both groups of women. No significant differences in the plasma levels of estrone, estradiol, or estrone sulfate were detected between breast cancer and normal subjects. It is concluded that, given similar concentrations of estradiol in plasma of normal and breast cancer subjects, the significant increase found in the unbound estradiol fraction may result in a very small increment in tissue exposure to estrogens in breast cancer subjects. However, even such a small increase in tissue exposure to estradiol may be significant, given the length of time required for breast tumor development.

Topics: Aged; Body Weight; Breast Diseases; Estradiol; Estrone; Female; Humans; Menopause; Middle Aged; Sex Hormone-Binding Globulin