Trilostane, an effective signal transduction inhibitor for advanced ER+ve and ER-ve post-menopausal breast cancer

Abstract

540 Background: Acquired endocrine resistance to both SERMs and AIs, is a major clinical problem and a leading cause of treatment failure in post menopausal women with advanced breast cancer. Trilostane (Modrenal) has been shown to modulate binding of estrogen to both estrogen receptor alpha (ERa) and estrogen receptor beta (ERβ) and block cell proliferation in breast cancer cells mediated through both ERE and AP1-dependent pathways. Methods: A total of 714 post-menopausal women with assessable progressing advanced breast cancer were treated with trilostane in eleven centers world-wide. All patients had received prior endocrine and/or chemotherapy. Results: Of the 714 patients, 616 (86%) were known or assumed to be ER+ and of these, 164 (27%) had an objective response (OR = CR + PR = 3 mths) and a further 65 (10%) had disease stabilisation (DS = 6 mths), giving an overall clinical benefit rate (CBR) of 37%. Within this ER+ cohort, 453 patients received trilostane for >12 weeks and achieved an OR of 36% an...