Background: PERSEPHONE is a randomised controlled trial comparing six months of trastuzumab to the standard 12 months in patients with HER2 positive early breast cancer. Methods: 4,000 patients will be randomised into the two arms (1:1). The power calculations assume that the disease-free survival (DFS) of standard treatment (12 months trastuzumab) is 80% at 4 years. Randomisation of 4,000 pts will allow the trial to prove non-inferiority of six months trastuzumab (5% 1-sided significance & 85% power). Non-inferiority is defined as ‘no worse than 3%’ below the control arm (12 month) 4 year DFS. Primary outcome is DFS, and secondary outcomes are overall survival (OS) non-inferiority; cost effectiveness; cardiac function & quality of life. Tumour blocks are collected to research molecular predictors of survival with respect to duration of trastuzumab treatment. Blood samples are analysed for single nucleotide polymorphisms (SNPs) as pharmaco-genetic determinants of prognosis, toxicity and treatment outcome. Exciting developments led to a protocol amendment (Dec 2013) which allows sites to administer IV or sub-cutaneous trastuzumab according to their standard practice. Cardiology data on the first 2,500 patients is now being analysed. PERSEPHONE is funded by the NIHR HTA programme in the UK. Results: PERSEPHONE commenced recruitment in October 2007. At abstract submission, 3,166 pts (79%) had been randomised from 154 UK sites. Recruitment is due to complete mid-2015 with the first planned interim analysis of the primary outcome mid-2016. The iDMSC reviewed all data available on HERA and PHARE in 2012 as well as a PERSEPHONE interim analysis. There were no safety findings or signals that would warrant a change of the study plan & the high quality of data was noted. Conclusion:PERSEPHONE continues the active recruitment phase as planned with the sub-cutaneous form of trastuzumab proving popular. Publication of early PHARE results have reinforced interest in the PERSEPHONE trial both nationally and internationally. There has been full support from the Breast International Group (BIG) and the international breast cancer community to answer this important shorter duration question. Clinical trial information: 52968807.