A look at how redefining triple negative breast cancer could help improve treatment of the disease.
Triple negative breast cancer (TNBC) is defined as a type of breast cancer where the cells lack three proteins (estrogen receptor, progesterone receptor and HER2 receptor) commonly associated with other types of the disease. The most successful targeted treatments for breast cancer are designed to attack cancer cells with at least one of these proteins. So where does this leave women with TNBC, whose breast cancer can’t be targeted as effectively? Dr Matthew Lam explores this complex area and the research that is changing how we see TNBC.
Standing out in the crowd
Currently, women with TNBC have to rely solely on chemotherapy, radiotherapy and surgery to treat their breast cancer. All of the studies that have been conducted to test targeted treatments against TNBC have failed at some stage in the process and this may be due to the problem with how we define TNBC. The category has become a bit of a dumping ground for any breast cancer which doesn’t fit into any other clinical definition. The result is an extremely diverse groups of patients, including pockets of people warranting different treatment options, all being treated the same way.
As a result of this over-simplification, a drug tested on a ‘triple negative’ group may fail, but within that population there may be some who do benefit because of a specific characteristic of their cancer. These people become lost in the crowded statistical marketplace and so any positive effects of the drug become masked. It’s only by refining how we define TNBC patients that we’ll begin to improve their treatment options.
One size does not fit all
In 2011, research carried out by scientists in the US revealed that TNBC could be broken down into six different types and that some of these sub-types displayed characteristics which could be targeted with drugs. It’s this kind of information we need to utilise in the design of clinical trials so that, instead of treating these patients as one homogenous group, we start targeting the right therapy towards the right sub-group of women.
Researchers have also discovered that several proteins are produced at an abnormally high level in some TNBC patients. So far, none of these proteins have led to a breakthrough in targeted treatments, but hope may lay in a group of proteins called FGFRs.
FGFRs are found to be abnormal in around 12% of triple negative tumours, and play an important role in driving the growth of these tumours. Studies have shown FGFRs to be a potential therapeutic target for cancer, so screening TNBC patients for FGFR abnormalities could help identify people who would benefit from FGFR-targeted therapies.
Breakthrough’s approach to TNBC
Research led by Professor Andrew Tutt at the Breakthrough Research Unit at Kings College London is looking for particular genetic or molecular ‘flags’ which could be used to help design new therapies or select the right treatment for an individual patient. The team’s research has found several of these flags which help refine our definitions of TNBC and emphasise the need for new approaches to improve diagnosis of this group of patients.
Andrew is also leading a study called the Triple Negative Trial, which aims to work out which of two chemotherapy drugs works best for women with TNBC. As this is the only current option for these patients, it’s vital that doctors know which drug to prescribe.
Initial data from this study, presented at a conference in San Antonio, showed that there wasn’t any difference in benefit between the two drugs, meaning it’s unlikely to have any impact on treatment. However, the really interesting result came when they began to divide patients into smaller sub-groups. For patients who tested negative for a faulty BRCA gene, the drug carboplatin gave a significant benefit over docetaxel. This shows how even refining our definition of TNBC by one degree (faulty BRCA or not) could help guide treatment choice.
Delving deeper into TNBC
Major advances in technology means that we can now decipher the genetic code of a patient’s cancer quicker and cheaper than ever before. This is driving research forward at a tremendous pace and as we delve deeper into the genetics of TNBC we will begin to improve outcomes for patients.
Eventually we will stop looking at TNBC as what it isn’t and start seeing what makes individual patients stand out. This will be the key to offering better treatments for TNBC patients, who currently miss out on the targeted therapies that have been extremely successful for other types of breast cancer.
Dr Matthew Lam is Breakthrough Breast Cancer's Senior Research Officer