Human breast cancer tissue is able to concentrate estrogens. 17-beta-estradiol (E2) and estrone (E1) are produced locally through several mechanisms, e.g. from conjugated and unconjugated steroid hormones uptaken from the circulation. This study was aimed to investigate the correlation between endogenous serum sex steroid concentrations and tumour receptor status in postmenopausal breast cancer patients undergoing surgical intervention. The study involved 740 postmenopausal patients with primary breast cancer of Stage I-II prior to surgical intervention. None of them took hormone preparations and received chemo or radiotherapy. Serum levels of sexual hormones and precursors, sex hormone-binding globulin (SHBG), insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) were measured by fully automated equipment using RIA and IRMA methods. Estrogen (ER) and progesterone receptors (PR), HER2/neu expression in tumour tissues were determined using immunohistochemical methods (NCL-ER-6F, 11/2; NCL-L-PgR-312; CB11-RTU, Novocastra; Hercep Test, DAKO). In the ICH 2+/3+ cases HER2/neu gene amplification was confirmed by fluorescence in-situ hybridization. MedCalc Software was used for statistical analysis. Our investigation revealed significant correlations among steroid receptor status of tumour tissue and the serum E1 and androstenedione (AD) levels. Close relationship was observed among serum value of E1-sulfate, IGF-1, testosterone (TE), dehydroepiandrosterone sulphate (DHEA-S) and HER2/ER status of tumour tissue. Results demonstrate that the positivity of tumour tissue receptor status can be predicted on the basis of increased serum unconjugated (E1, DHEA, AD, TE) and conjugated (E1-S, DHEA-S) sexual hormone concentrations. It is suggested that circulating E1-S and DHEA-S might play a major role in the intratumoral estrogen synthesis. Our study supports the hypothesis that the serum E1, AD, E1-S, DHEA-S, TE and IGF-1 levels might also be useful for predicting the magnitude of response to postoperative chemotherapy.
This research was supported by the Hungarian Research Fund (OTKA No.T 049814).