The role of HER family gene mutations and other abnormalities in HER2-amplified breast cancer resistance to HER2-targeted therapies

Key Information

Cancer type: 
Research Institution: 
RCSI & Beaumont
Grant Amount: 
Start date: 
October 1, 2011
End date: 
September 30, 2014

Scientific Project Abstract

There are different types of breast cancer, and one form, called HER2-positive breast canncer because of a protein called HER2 that it contains, is more aggressive than most other types of breast cancer. HER2-positive breast cancers account for as many as 1 in 5 of all cases of breast cancer. When treated with chemotherapy, women with HER2-positive breast cancer are much more likely to have their cancer come back and are therefore much less likely to be cured than women with other types of breast cancer. Our ability to treat HER2-positive breast cancer improved recently when new drugs that block the HER2 protein were discovered' these drugs are called trastuzumab and lapatinib. However, the problem is that these drugs only work in a subset of women with HER2-positive breast cancer. When these drugs do not work it is because the cancer cells find a way to escape from being killed by these drugs. This is called treatment resistance. While we currently know the reasons why some HER2-positive breast cancers are not killed by these drugs, in a lot of cases we still simply don't know why the cancer cells are resistant. We have very recently found some new changes in the genes of breast cancer cells, called mutations, and we want to see how often these new mutations happen in HER2-positive breast cancer as well as other gene abnormalities that we already know about. We think that these mutations might be a reason that some HER2-positive breast cancers are resistant to the new drugs above and we want to test this. We think that women with HER2-positive breast cancer in which the cancer cells have these new mutations are much less likely to be cured with current treatments and we will test this in our study. We also want to see how these new mutations work in cancer cells, and if they can tell us which drugs are best for which patients, so that we can make sure we are prescribing the right drugs to the right patients. If we can find out more about these new mutations, then we will likely be able to stop HER2-positive breast cancer becoming resistant to treatment by designing better treatment strategies so that women with aggressive HER2-positive breast cancer can live longer and have better lives.

For the non-scientist

One-line description: 
Examining the role of DNA mutations in drug resistance in breast cancer patients
What this project involves: 

HER2 positive breast cancer account for as many as 1 in 5 of all cases of breast cancer. There are a number of targeted drugs used to treat HER2 patients' however, these drugs only work on a subset of patients due to the development of drug resistance. The precise reason why this resistance develops is currently not known. The aim of this project is to examine DNA mutations which may be responsible for this drug resistance in HER2 positive breast cancer patients.