Measurement of estrone sulfate in postmenopausal women: comparison of direct RIA and GC-MS/MS methods for monitoring response to endocrine therapy in women with breast cancer.

BACKGROUND: High concentrations of estrone sulfate (EIS) are present in serum of pre- and postmenopausal women. Most assays for this estrogen conjugate involve enzyme hydrolysis and chromatographic purification prior to RIA. We have compared concentrations of serum EIS in postmenopausal women measured by direct RIA or GC-MS/MS methods. PATIENTS AND METHODS: We analysed serum EIS concentrations using a direct 'ultrasensitive' RIA. Serum EIS concentrations were also measured by GC-MS/MS in which estrone conjugates are isolated using a solid-phase technique after which enzyme hydrolysis is employed to liberate estrone prior to GC-MS/MS analysis. RESULTS: We analysed 32 serum samples collected from 8 postmenopausal women participating in a Phase I trial of the steroid sulfatase inhibitor 667 COUMA TE. Concentrations of E1S were 998+/-86 pmol/l (mean +/- sem) and 912+/-114 pmol/l as measured by direct RIA and GC-MS/MS methods respectively. There was a highly significant correlation (r=0.96, p<0.001) between concentrations of EIS measured by the different methods. CONCLUSION: We conclude that the direct 'ultrasensitive' RIA for the measurement of serum EIS provides a reliable method for assaying serum concentrations of this estrogen conjugate and should be useful in monitoring the response to endocrine therapy in postmenopausal women with hormone-dependent breast cancer.