Researchers from the Wellcome Trust Sanger Institute and their collaborators have discovered that a greater number of breast cancers are genetically similar to rarer cases with faulty BRCA1 or BRCA2 genes.

Monday 13 March 2017      Research
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HRDetect is a new computer-based tool used to identify patterns of mutations

The results, published today (13 March) in Nature Medicine, open up the possibility of up to 20 per cent of women being treated with PARP inhibitors, a class of drug – currently in trials – that has previously only thought to be effective for women with an inherited BRCA1 or BRCA2 mutation.

In the study, researchers analysed the breast cancer genomes of 560 patients and looked for every single type of mutation possible. The team developed a new computer-based tool called HRDetect to identify patterns of mutations – mutational signatures – in the tumours which were similar to people who have mutations in the BRCA1 and BRCA2 genes.

Scientists discovered that many breast cancer patients had mutational signatures that were identical to people with faulty BRCA1 and BRCA2 genes, even though they had not inherited the mutations.

Baroness Delyth Morgan, Chief Executive at Breast Cancer Now, said:

“PARP inhibitors are a very promising treatment on the horizon and the suggestion that more patients may be able to benefit from them is greatly exciting.

“Crucially, this study is an early but encouraging step towards being able to offer women treatments targeted to the genetic make-up of their breast cancer.

"The discovery that many women may have tumours genetically similar to patients with faulty BRCA genes, without them actually having a BRCA mutation, is somewhat of a revelation. We hope it could now lead to a watershed moment for the use of mutational signatures in treating the disease.

“Further investigation is needed to fully understand the clinical implications of these findings for future patients. But this study firmly opens the door for trials to assess whether up to one in five patients might benefit from PARP inhibitors.”

On the development of HRDetect, Baroness Delyth Morgan added:

“These first results from HRDetect are very promising. Further testing of this tool in a larger population will help to give a more accurate estimate of the proportion of patients with this mutational signature.

“That said, HRDetect involves the costly reading and sequencing of all the DNA in a cancer cell, so it is as yet unclear how long it may take for this tool to progress outside of a trial setting.”