New approach to treating breast cancer uses existing chemo drug

May 1 2006

British scientists say women who develop breast cancer because of two common genetic mutations could have their treatment transformed by a chemotherapy drug which already exists.

The drug Carboplatin which is currently used to treat ovarian and lung cancers may very well be as much as 20 times more effective than standard therapies for breast tumours triggered by defects in the BRCA1 and BRCA2 genes.

The scientists say that animal studies have indicated that Carboplatin,a platinum-based drug not normally used in breast cancer treatment, can target the "Achilles' heel" of tumours caused by BRCA defects.

They say their research with 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.

As many as 85 per cent of women who inherit mutations in one of these genes will develop breast cancer by the age of 70, and between them they account for 5 per cent of the 41,700 cases diagnosed in Britain each year which occur in women with a strong family history of the disease.

Some groups have a higher risk of having faults in these genes; around one in 44 Ashkenazi Jews carry a change in their BRCA genes compared to less than one in 100 people in the non-Jewish population.

Despite improvements in detection and treatment of early breast cancer, around 25% of women are likely to have a recurrence of their cancer.

The team are presently 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.

Women who have been diagnosed with a faulty BRCA1 or 2 gene and whose breast cancer has returned elsewhere in the body will be eligible.

Women from the UK, Europe, America and Australia will take part in the four year study.

They will be treated with Carboplatin or the best current treatment, the chemotherapy drug, Docetaxel.

Clinical trials are already under way and should they indicate that Carboplatin performs the same in the women as in the mice, 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, says breast cancer is not just one disease and different types of tumour will respond differently to particular drugs.

He says the genetically tailored chemotherapy treatment acts in a much more focused manner than standard chemotherapy.

Dr. Tutt and his collaborators, Dr. 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 makes them more vulnerable to Carboplatin.

The research may one day lead to improved quality of life and survival for women with this rare but important form of genetic breast cancer.

Dr. Mackay says the trial is unique because it is the first to treat a specific genetic population of breast cancer patients.

He hopes this will mean an improved quality of life and survival for women with this rare but significant form of genetic breast cancer.

There is currently there is no specially tailored chemotherapy treatment for women with faulty BRCA genes who have recurrent breast cancer, and such patients receive standard chemotherapy which is not always effective and can have unpleasant side effects.

Patients interested in signing up for the trial need to have a known fault in either BRCA1 or BRCA2, have a cancer that has spread beyond the breast and lymph glands and for which surgery is not suitable.

They must also not had any chemotherapy since the cancer spread.