Background
MBC, gastrointestinal adverse, breast cancer
METASTATIC BREAST CANCER, DISEASE, BREAST CANCER
Metastatic breast cancer (MBC) is oestrogen receptor (ER) positive in around 75% of cases [Multiple mechanisms of endocrine resistance exist, but one pathway may be through Src activation. Src is a non-receptor tyrosine kinase which is involved in multiple oncogenic pathways with implications for disease activity and therapy resistance [Saracatinib (AZD0530) is a potent and selective oral inhibitor of Src kinase. It enhances the anti-proliferative effect of endocrine agents in breast cancer models, thereby preventing endocrine resistance development and restoring sensitivity of resistant models to oestrogen deprivation [Phase I trials indicate that saracatinib is well tolerated with mainly gastrointestinal adverse events. Drug half-life is ~ 40–45 h and it is 90% protein bound in plasma with a large volume of distribution [This study was designed to test the hypothesis that the addition of a potent Src inhibitor (AZD0530) to conventional aromatase inhibition would improve outcomes in post-menopausal women with advanced incurable breast cancer. Based on the molecular basis of AZD0530, the presumed mechanism would be by delaying and/or reversing endocrine resistance.