DNA test may benefit women with hard-to-treat breast cancer

Genetic testing could reveal a subset of patients with aggressive breast cancer who would benefit from a non-standard treatment, a clinical trial has found. 

Patients with certain genes responded twice as well to treatment with the alternative drug carboplatin, according to the trial, published last week in the journal Nature Medicine. The study was a randomised controlled phase III trial, with 376 patients taking part in the study from 74 hospitals across the UK. 

The usual hormone drugs and targeted therapies for breast cancer act on three surface proteins. Tumours that lack all three receptors are known as triple-negative breast cancers and are among the hardest to treat. The standard treatment for triple-negative patients in the UK is the chemotherapy drug docetaxel. 

These results, however, show that triple negative patients with mutations in their BRCA1 or BRCA2 genes – which increase the risk of developing breast cancer – did better when receiving carboplatin. 

In this trial, two-thirds of triple-negative patients with faulty BRCA1 or BRCA2 genes showed a positive response to carboplatin, compared with only a third to docetaxel. A third of patients who did not have the faulty genes responded to carboplatin. This finding could help some triple-negative breast cancer patients. 

The researchers believe that the differences are due to how the two drugs work. Docetaxel attacks part of the machinery that cells use to divide, while carboplatin directly binds to and interferes with DNA itself. As the BRCA1 and BRCA2 genes are usually involved in repairing damaged DNA, the researchers believe that a tumour in a patient with a less functional version of either BRCA gene is more susceptible to carboplatin, as less of the DNA damage it causes can be repaired.

About 15 percent of breast cancer cases are triple negative, of which five to 15 percent are likely to have BRCA1 or BRCA2 mutations. It is not currently standard practice to test women with triple-negative breast cancer for BRCA mutations, something that the authors of this study believe should change.  

'Using this simple test enables us to guide treatment for women within this type of breast cancer,' said Professor Andrew Tutt of the Institute of Cancer Research in London and lead author of the study. 'This is a great example of using personalised genetics to repurpose a chemotherapy drug into a targeted treatment.'