Today I will summarise my talk about the HER2DX genomic test. This is a new assay that is clinically available and this assay is the consequence of ten years of research in early-stage HER2 positive breast cancer where we have learned that we need tools to help us optimise systemic therapies, not only in the neoadjuvant setting but also in the adjuvant setting in small tumours like stage 1. 

HER2DX is an assay that builds upon ten years of research. It is based on the expression of 27 genes, 27 genes that recapitulate four main biological features of HER2 positive breast cancer. On the one hand we have the immune signature which represents 14 genes among the 27. Then we have a proliferation signature, a luminal signature and also the expression of HER2 and the HER2 amplicon. 

With these four biological variables, together with the tumour stage and nodal stage, HER2DX provides three types of information. On the one hand it provides a prognostic score, we call it the HER2DX risk score. It was trained using these six variables, the four biological and the two clinical, to predict long-term outcome in early-stage breast cancer. This might be especially useful in stage 1 disease where we need to make decisions in the clinic whether to indicate the use of a single taxane and one year of trastuzumab versus the standard of care in the past for most patients which was multiagent chemotherapy and one year of trastuzumab. 

Also in stage 1 we must acknowledge the very small tumours, less than 1cm, where the evidence of using trastuzumab or chemotherapy is vague. Therefore, having a prognostic tool might help make better decisions regarding what type of systemic therapy for these very small tumours, less than 1cm, node negative. 

Also, the HER2DX, as I said, provides three types of information. One is the risk score, as I mentioned, the other one is the pCR score, this is a score that talks about the probability of achieving a pathological complete response after trastuzumab-based neoadjuvant therapy. The score has been validated across many different studies. Basically, this will help mostly in stage 2, stage 3 disease, where knowing the pCR score helps escalate the amount of chemotherapy or de-escalate the amount of chemotherapy and just treat patients with a single taxane, trastuzumab and pertuzumab. In fact, in the DAPHNe trial we validated retrospectively and showed that if you are pCR high, which is around one third of the patients, the probability of achieving a pathological complete response with THB 3 months is 92%. So in this particular scenario, stage 2, stage 3, that’s where the clinical utility resides.

Finally, we provide also the levels, individual levels, of Rb2 mRNA score by itself. They are useful for predicting the true clinical status of HER2, HER2 positive versus HER2 negative. But also we have validated Rb2 mRNA as a predictor of response to anti-HER2 therapy in the absence of multiagent chemotherapy. This has been a retrospective validation in trials such as the PAMELA trial or the PER-ELISA.

So overall the HER2DX assay today provides clinically meaningful information in early stage HER2 positive disease that will help, and is helping today, make better treatment decisions for patients. Thank you very much.