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WOMEN who develop breast cancer because of two common genetic mutations could have their treatment transformed by an existing chemotherapy drug.
Animal studies have indicated that carboplatin, currently used to treat ovarian and lung cancers, could be up to 20 times more effective than standard therapies for breast tumours triggered by defects in the BRCA1 and BRCA2 genes.
Up to 85 per cent of women who inherit mutations in one of these genes will develop breast cancer by the age of 70, and they together account for 5 per cent of the 41,700 cases diagnosed in Britain each year.
British scientists have now discovered that carboplatin, a platinum-based drug not normally used in breast cancer treatment, can home in on the “Achilles’ heel” of tumours caused by BRCA defects. Research in mice has shown that cancer cells with BRCA2 mutations are twenty times more sensitive than normal to carboplatin, and that BRCA1 tumours are between five and twenty times more sensitive.
The scientists are recruiting 150 BRCA breast cancer patients, 75 with each mutation, who will be treated with carboplatin or docetaxel, the standard chemotherapy agent for the disease, to determine which is more effective. Clinical trials start today. If the study shows carboplatin performing as the animal work indicates, it could be given routinely to breast cancer patients with BRCA mutations within five years.
Andrew Tutt, consultant oncologist at Guy’s and St Thomas’ NHS Foundation Trust in London, who is leading the trial, said: “There is an increasing realisation that breast cancer is not just one disease, but that different types of tumour will respond differently to particular drugs. This genetically tailored chemotherapy treatment acts in a much more focused manner than standard chemotherapy.”
Dr Tutt and his collaborators, James Mackay, of University College London, and Max Parmar, of the Medical Research Council clinical trials unit, are supported by Breakthrough Breast Cancer and Cancer Research UK.
All cancers are caused by copying mistakes in DNA, which cause cells to start dividing uncontrollably, and BRCA1 and BRCA2 are essential to repairing these errors.
Two copies of each gene are inherited, one from each parent, but when one copy is mutated the other has no back-up, making cancers more likely to develop.
The resulting tumours have no working copy of the DNA repair gene at all, while the healthy tissue around them has one normal copy. This appears to make them more vulnerable to carboplatin.
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