The steroid sulfatase inhibitor BN83945 inhibits the E1S stimulated growth of DMBA induced mammary tumors in rat

Abstract

14683 Background: Steroid sulfatase (STS) is a new target for the treatment of steroid hormone-dependent diseases such as breast, prostate or endometrial cancer. In breast cancer, estrogens play a major role in the establishment of the disease and between one to two- thirds of tumours are estrogen receptor (ER) positive. Despite current hormonal treatments, improvement is still necessary to achieve better disease control & improve disease outcome. BN83495 is a non-steroidal, non-estrogenic, potent, irreversible STS inhibitor that blocks both the formation of E1 from estrone sulfate (E1S) and androstenediol from DHEAS. Methods: The ability of BN83495 to inhibit E1S- stimulated tumor growth in the rat was examined in a DMBA-induced mammary tumor model. Results: Based on median tumor volume and the interquartile range at the end of the treatment period, BN83495 displayed the greatest antitumor activity compared to Tamoxifen or Fulvestrant. Addition of Fulvestrant or Tamoxifen to BN83495 did not improve on the potent antitumor activity already observed with BN83495 alone. Pharmacokinetic data of BN83945 and estradiol levels were generated during this study and are discussed. Conclusions: Altogether, these preclinical results have supported the entry of BN83945 into further clinical trials for estrogen receptor- positive breast cancer patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Ipsen