Poster Presentation 25th Lorne Cancer Conference 2013

A Myc transcriptional program that is independent of EMT drives a poor prognosis tumour- propagating phenotype in HER2+ breast cancer (#289)

Radhika Nair 1 , Sandra O'Toole 1 , Alexander Swarbrick 2
  1. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  2. The Garvan Institute of Medical Research, Darlinghurst, NSW, Australia

The HER2 (ERBB2) and MYC genes are commonly amplified genes in breast cancer, yet little is known about their molecular and clinical interaction. Using a novel chimeric mammary transgenic approach and in vitro models, we demonstrate markedly increased self renewal and tumour propagating capability of cells transformed with Her2 and c-Myc independent of an EMT programme. Co-expression of both oncogenes in cultured cells led to a pronounced activation of a c-Myc transcriptional signature. We show that HER2 and c-MYC are frequently co-amplified in a clinical breast cancer cohort and that co-amplification is strongly associated with aggressive clinical behaviour and poor outcome. Lastly, we show that in patients receiving adjuvant chemotherapy (but not targeted anti-HER2 therapy),MYC amplification is associated with a poor outcome in HER2+ breast cancer patients. These findings demonstrate the importance of molecular context in oncogenic transformation and acquisiution of a malignant stem-like phenotype and have important diagnostic and therapeutic consequences for the clinical management of HER2+ breast cancer.