Abstract

Presurgical treatment of breast cancer provides a unique opportunity to link biology and clinical variables as well as becoming an attractive scenario for drug development. We have validated the proliferation marker, Ki67, as an intermediate end-point of efficacy for endocrine therapy as early as 2 weeks after starting treatment. A variety of immunohistochemical and genomic analyses have enabled us to make several novel biological observations including on a new index of oestrogen regulated genes (AvERG), the coordinated expression of genes adjacent to ESR1 and the close relationship between hypoxia and proliferation. In each circumstance it has become clear that the extreme heterogeneity of ER+ breast cancer requires large numbers of correlative data for confident definition of associated factors and subgroup. To enable this we have recruited over 900 patients with ER+ breast cancer to the PeriOperative Endocrine Therapy for Individualising Care (POETIC) trial of presurgical aromatase inhibitor treatment. Total recruitment will be 4,000 and will provide an opportunity to markedly enhance our understanding of ER+ breast cancer in patients.