Familial breast cancer BRCA trial 02/05/06. By the Public Health Genetics Unit A new international phase II clinical trial is to look at the effect of a novel form of drug treatment for metastatic hereditary breast cancer.

More than three-quarters of all cases of familial breast cancer occur in individuals with mutations in the BRCA1 or BRCA2 genes, in whom the tumours are often more advanced than in other breast cancer patients, and around a quarter will have a recurrence of cancer following initial treatment.

The new four-year BRCA trial , led by Breakthrough Breast Cancer and Cancer Research UK, will monitor around 150 women from the UK, Europe, America and Australia, who have BRCA1 or BRCA2 mutations and in whom an initial breast cancer has been followed by recurrence at another site in the body, other than the lymph glands.

Standard chemotherapy with docetaxel will be compared with the use of carboplatin, a platinum-based drug currently used for the treatment of ovarian (but not breast) cancer, for toxicity, response and time to progression.

This is the first trial to treat a specific genetically defined subpopulation of breast cancer patients; knowledge of the normal functions of the BRCA1/2 proteins in DNA repair suggested that tumours with mutations in the BRCA genes might be particularly sensitive to platinum-based drugs, which induce cross-linking between DNA molecules, and studies have supported this theory.

The use of carboplatin may therefore prove to be effective in the treatment of BRCA1/2 tumours and, since the patient's normal tissues retain functional copies of the BRCA proteins, the drug should in theory target the tumour cells specifically, reducing the toxic side-effects.

Researcher Dr Andrew Tutt from Guy's and St Thomas' Hospital said: "This genetically tailored chemotherapy treatment, carboplatin, acts in a much more focused manner than standard chemotherapy…While standard chemotherapy can affect any rapidly growing cell, these platinum drugs seem to be much more effective in destroying the cancerous BRCA cells. We hope this will mean improved quality of life and survival for women with this rare but important form of genetic breast cancer." (See Genetic breast cancer drug hope , BBC news report: 1 May 2006.)

Article courtesy of the Public Health Genetics Unit .