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Hormone sensitive breast cancer (BC) is a common disease in postmenopausal women. Generally seen as less aggressive than other BC subtypes patients have a continued risk of relapse for 15+ years (EBCTCG, 2011) thus the cumulative risk is not insubstantial. Efforts continue to identify patients who are at continued residual risk of relapse in order to develop new treatment strategies. Previous trials (IMPACT, 2007) suggested that aromatase inhibitor (AI) treatment for 2 weeks in the peri-surgical window-of-opportunity results in detectable biomarker changes (Ki67) and predicts long term outcome. Gene expression profiling offers opportunities to identify patients demonstrating early resistance to endocrine therapy. POETIC was a UK-wide RCT devised to provide definitive results on the role of perioperative (AI) treatment. Biopsies were taken at diagnosis and 2 weeks later at surgery thus allowing an in vivo assessment of AI sensitivity. To succeed, POETIC needed to overcome substantial barriers in relation to compliance with cancer wait times, recruitment of women at diagnosis, varied clinical practice and to ensure receipt of sufficient quality tissue samples for analysis of biomarker endpoints. Patient advocates were involved from inception. POETIC succeeded in recruiting 4486 women from 130 UK centres. Paired tissue samples were received for 96% patients. Lessons learnt in rolling out the world's largest window-of-opportunity BC trial illustrate the viability and potential of this experimental model as a vehicle for testing early biological effects of novel agents and to identify women most likely to be at long term residual risk of relapse.

TNT is a trial comparing carboplatin with docetaxel for advanced TN or BRCA1/2 BC patients. TNBC is heterogeneous; median progression-free survival (PFS) is short but some patients have prolonged PFS following treatment. BRCA1/2 patients were hypothesised to respond better to carboplatin. This interaction, with the heterogeneous population, was expected to cause a failure of PH assumptions required for Cox-PH analysis. Therefore, TNT required alternative analysis methods.