Testing tumours for the breast cancer gene BRCA1 could be a powerful way of predicting how patients will respond to chemotherapy, scientists from Breast Cancer Campaign and Cancer Research UK report.
The BRCA1 gene plays an important role in stopping cancer developing, and women who inherit a damaged version of the gene have a high risk of developing breast cancer. BRCA1 may also get switched off in as many as 30 per cent of tumours, even in patients who inherited a normal version of the gene.
Now researchers have found that tumour cells react differently to chemotherapy depending on how well BRCA1 is working within them. The findings could yield a new test to help doctors decide which treatment to use on breast cancer patients, and the researchers will soon put the results to test as part of a patient trial.
The main researchers on the project were Dr Jennifer Quinn, Dr Paul Harkin and Dr Richard Kennedy, all based at the Cancer Research Centre, Queen’s University Belfast.
The research team found that a functional BRCA1 gene made breast cancer cells 10 to 1,000 times more resistant to one type of drug (drugs that work by damaging DNA within cancer cells).
In contrast, functional BRCA1 made cells over 1,000 times more sensitive to a second type of drug (drugs that work by blocking cell division).
These results suggest that testing tumours to find out if BRCA1 is working properly could help doctors decide which type of chemotherapy treatment to use. Cancers in which BRCA1 is working properly may be treated more successfully by drugs blocking cell division. And cancers in which BRCA1 is faulty or has ceased to work properly could be better treated with drugs that damage cancer cell DNA.
Targeting chemotherapy in this way could make the treatment more effective and reduce its side effects, and could be particularly important for those patients who inherit a defective copy of BRCA1.
Cancer Research UK’s Dr Paul Harkin, the senior researcher on the study, says: “Our results were quite dramatic. Essentially, cancer cells with functional BRCA1 are highly resistant to one type of chemotherapy but extremely sensitive to another.
“For scientists like myself it’s very exciting, because knowing a tumour’s BRCA1 status may be invaluable in deciding which type of chemotherapy to use.”
Fellow researcher Dr Jennifer Quinn, of Breast Cancer Campaign, says: “Breast cancers can differ greatly from one woman to the next, so finding ways of matching a treatment to a patient is one of the key areas of current research.
“Our study is part of a movement towards a new approach to breast cancer, in which women will be treated on the basis of information gathered about their individual tumours.”
Pamela Goldberg, Chief Executive of Breast Cancer Campaign says: “With this research we will be moving towards a situation where drug therapies could be specifically targeted at the individual tumour delivering more effective treatments. We are very excited by the potential near term benefits to patients and the avenues for research generated by these results.”
Professor Robert Souhami, Director of Clinical Research at Cancer Research UK, says: “It’s intriguing that a single gene should have such important effects on the way cancer cells respond to treatment.
“We must now await results from clinical trials with patients, to make sure that the expression of the gene really does predict the likelihood of responding to certain drugs. But there’s no doubt that this discovery could have significant implications for the future of breast cancer treatment.”
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The publication of this research coincides with the launch in Northern Ireland of Breast Cancer Awareness Month.
The gene focussed upon in this study, BRCA1, is well known as an agent for inherited breast cancer. Up to 80 per cent of women who inherit a damaged version of BRCA1 will develop breast cancer at some point in their lives. Approximately one in 850 women in the UK inherit a faulty BRCA1 gene.
Up to five per cent of breast cancers result from inheriting a faulty version of BRCA1.
The researchers tested two types of drug: one type that works by directly damaging the genes of cancer cells, and another type that blocks cell division by preventing the separation of the genetic material into two parts. Both types of drug cause cancer cells to die. Researchers compared the effectiveness of both types of drug in cells in which BRCA1 works properly, and others in which it does not.
Examples of cancer drugs that cause DNA damage are bleomycin, cisplatin and etoposide. Examples of cancer drugs targeting cell division are paclitaxel and vinorelbine.
The researchers on the project are making progress at understanding what causes the effects they have seen. It is already known that BRCA1 can help repair damaged DNA – and it may be this ability that makes cancer cells which have defective BRCA1 more sensitive to DNA damaging drugs.
The research was funded by Cancer Research UK, Breast Cancer Campaign and the Research and Development Office, NI.
