Molecular evolution of metastatic HER2-positive breast cancer

Approximately 20% of all breast cancers (BCs) are HER2-positive and this type of BC is particularly aggressive. Drugs that target HER2, such as trastuzumab (Herceptin), have improved our ability to treat HER2-positive BC. However, many women with HER2-positive BC are not cured following treatment, and more than 25% of women go on to develop incurable recurrent disease. In the laboratory, we have shown that another cancer causing protein called phosphatidylinositol-3-kinase (PI3K) allows some HER2-positive BCs to survive despite cancer cells being treated with trastuzumab. Copanlisib is a drug that blocks PI3K. We have HER2-positive BC cells which have been made resistant to trastuzumab, and we have shown that when we treat these cells with both trastuzumab and copanlisib the cancer cells die. Therefore, we are running two clinical trials to show that copanlisib given with trastuzumab or another drug targeting HER2 called T-DM1 is a safe and effective new treatment for women with incurable trastuzumab resistant HER2-positive BC.

In this study we want to determine how metastatic HER2-positive BCs, that are resistant to trastuzumab, change when patients are given copanlisib in combination with trastuzumab or T-DM1. Using this information we will determine in which women these treatment combinations will work best. We will use tumour tissue and blood samples that are collected from patients who are being treated with these drug combinations to get a better understanding how the BC cells in these women change over time as a result of treatment. We will try to determine the changes that will predict which women will respond best to copanlisib, and the changes that occur in a patients cancer cells that ultimately result in their cancer growing again. We will then use that information to test and find further new effective treatments for treatment-resistant metastatic HER2-positive BC that is currently incurable.

Award Date
27 June 2019
Award Value
Principal Investigator
Professor Bryan Hennessy
Host Institution
Royal College of Surgeons in Ireland
Investigator Led Projects