Professor Sir Mike Stratton, director of the Wellcome Trust Sanger Institute where the research took place, said that this type of analysis could point to “the complete set of cancers that will respond to certain drugs that are already known to be effective in a subset”. He called the findings a “promising start”, but added that further DNA analysis was needed to confirm the findings.
Breast cancer is the most common cancer in the UK, with more than 55,000 people diagnosed each year. Between 1 and 5% of breast cancers are caused by inherited faults in the BRCA1 or BRCA2 genes. These faults stop cells repairing their DNA when it becomes damaged, which raises the risk of certain types of cancer, particularly breast and ovarian.
The scientists found a ‘signature’ in the DNA of a number of breast cancer samples that suggests they are genetically similar to tumours caused by BRCA1 and BRCA2 faults. Based on these estimates, published in the journal Nature Medicine, they believe many more women than previously thought could benefit from PARP inhibitors. PARP inhibitors specifically kill cancer cells by targeting a molecule they become reliant on to repair their DNA. One PARP inhibitor, called olaparib (Lynparza), has been approved by NICE for some women with ovarian cancer. The drug is still being tested in clinical trials for breast cancer.
Dr Serena Nik-Zainal, lead author from the Wellcome Trust Sanger Institute, said: "Our study shows that there are many more people who have cancers that look like they have the same signatures and same weakness as patients with faulty BRCA1 and BRCA2 genes. We should explore if they could also benefit from PARP inhibitors.”
Previous research indicated that genetic faults other than those in BRCA1 and BRCA2 could leave tumours vulnerable to the drugs.
To search for ‘signatures’ that may reveal this susceptibility the Sanger team analysed the DNA of 560 breast cancer patients. Even in some patients without the inherited BRCA1 or BRCA2 faults, they found patterns similar to in those who had the errors, indicating that cells’ DNA repair machinery was faulty.
These signatures predicted that up to 22% of breast cancer patients sampled could benefit from PARP inhibitors; significantly more than the previously identified 1-5% with inherited BRCA1 and BRCA2 mutations.
Professor Ruth Plummer, a Cancer Research UK clinician at the Northern Institute for Cancer Research, at Newcastle University, said that the next step would be to test the findings in clinical trials to see if PARP inhibitors can treat women with this particular signature. “Research like this is incredibly important in helping as many patients as possible benefit from new treatments,” she said. “Similar signatures have also been found in ovarian cancer, suggesting that it isn’t only people with faults in their BRCA genes who could be treated with these drugs.”