Estrone sulfatase versus estrone sulfotransferase in human breast cancer: potential clinical applications.

Estrone sulfate (E1S) is concentrated in high levels in human breast cancer tissue. The values are particularly high in postmenopausal women and many times those circulating in the plasma. Also, the tissular concentration of this conjugate are significantly higher in tumoural tissue than in the area of the breast considered as normal. The enzyme which hydrolyzes E1S: sulfatase, as well as the enzyme which biosynthesises this conjugate: sulfotransferase, are present in significant concentrations in breast cancer tissue. Consequently, E1S is a balance between the activities of the two enzymes. As breast cancer tissue has all the enzymes necessary for the synthesis of estradiol (E2), and the formation of E2 from E1S 'via sulfatase' is the main pathway, it was very attractive to explore inhibitory agents of this enzyme. It was observed that different substances including antiestrogens (4-hydroxytamoxifen, ICI 164,384) and various progestins (promegestone, nomegestrol acetate, medrogestone) as well as Org OD14 (tibolone) can block the sulfatase activity. In addition, it was demonstrated that different progestins (medrogestone, nomegestrol acetate, TX-525) and org OD14 can stimulate the sulfotransferase activity for the formation of the biologically inactive E1S. It is concluded that the inhibition of sulfatase and the stimulation of sulfotransferase activity can open interesting possibilities to explore these effects in patients with breast cancer.