TAS-108 is a novel steroidal anti-oestrogen, expected to be useful for the treatment of breast cancer. The present study was conducted to investigate the safety, tolerability and pharmacokinetics of TAS-108 following the administration at a single oral dose of 40 mg to up to 120 mg in 12 post-menopausal women and the effect of food on the pharmacokinetics of the drug. All adverse events were mild and involved transient symptoms that resolved without therapeutic intervention. TAS-108 was readily absorbed and plasma levels of TAS-108 steadily declined, apparently in a multi-exponential manner. C max and AUC 0-12 were proportionally increased with increasing dose of TAS-108. The C max and AUC 0-t of TAS-108 and its metabolite, deEt-TAS-108, were significantly increased to approximately 150% when TAS-108 was administered after a meal. Food did not affect the elimination half-life of TAS-108 or its metabolites. In this escalating dose-study of TAS-108, the drug was well tolerated by healthy post-menopausal Japanese women. The pharmacokinetics of TAS-108 indicated dose proportionality, and its bioavailability was significantly increased by food intake.New breast cancer cases and deaths due to breast cancer reported in 2008 were estimated to be 184,450 and over 40,930, respectively, in the United States [1]. Although breast cancer incidence rates have continued to increase in Japan [2] to the same extent as in USA, the mortality rates have declined in these and several other countries during the 1990s due to more effective therapies and early detection of breast cancer [1,3]. Many chemotherapies and endocrine therapies have been used to treat breast cancer in the neoadjuvant and adjuvant setting as well as to prevent breast cancer. Endocrine therapy is a standard care for the treatment of post-menopausal women with oestrogen receptor-and/or progesterone receptor-positive breast cancer. Endocrine therapy in these patients is as effective as chemotherapy in terms of relapse-free status and overall survival, and its adverse effects are fewer and less severe than those of chemotherapy [3,4]. The selective oestrogen receptor modulator (SERM), tamoxifen, has been in use for the treatment of advanced breast cancer for more than 30 years and is currently a treatment option for all stages of oestrogen receptor-positive diseases regardless of the menopausal status of the patient [4,5]. As found from several large clinical trials such as the ATAC trial, , aromatase inhibitors such as anastrozole, letrozole and exemestane have been shown to be clinically superior to tamoxifen on the efficacy for post-menopausal patients. These inhibitors do not have the many risks [11,12] and they do not have favourable agonistic properties towards oestrogen receptors as long-term tamoxifen treatment [13,14], which has the preservation of bone mineral density and favourable effect on the cardiovascular risk in post-menopausal women. On the other hand, most breast cancer patients acquire resistance to tamoxifen after longterm use, as indi...