AI resistant patients were recruited from 19 UK sites and randomly assigned (1:1) to fulvestrant 500mg (day 1 and 15 of cycle 1 and day 1 only of subsequent 28 day cycles) with either vandetanib 300mg (f+v) or placebo (f+p) daily until disease progression, unacceptable toxicity or withdrawal of consent. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), safety, and the influence of RET signalling pathway component expression (e.g. total RET immunostaining) on vandetanib activity....high total RET protein expression was associated with a significant PFS advantage of 8.87m vs 3.94m in the low RET group (HR 0.493: 95% CI 0.32 to 0.77; p=0.002), which was independent of treatment arm.