New treatment targets inherited breast cancers

This latest piece of research provides an important target for drugs in treating breast and prostate cancers that are common in the US. According to the American Cancer Society, an estimated 217,440 Americans were diagnosed with breast cancer.

Nearly 41,000 UK women are diagnosed each year with breast cancer and, of those, about 5 per cent have strong hereditary factors, such as mutations in one of the two BRCA genes.

Women carrying faults in the BRCA1 and 2 genes have up to an 85 per cent chance of developing breast cancer by the age of 70. Currently there is no specific treatment available for these women.

The drug, known as a poly (ADP-ribose) polymerase (PARP) inhibitor, may be very effective in killing tumour cells in people who have faults in BRCA1 and BRCA2. The study also revealed that the drug is likely to be much less toxic to healthy cells than standard chemotherapy.

Breast tumours in women who inherit faults in either the BRCA1 or BRCA2 genes occur because the tumour cells have lost a specific mechanism that repairs damaged DNA (homologous recombination). PARP inhibitors selectively kill cells where this form of DNA repair is absent and so are highly effective in killing BRCA deficient tumour cells and other similar tumour cells. Normal cells are largely unaffected by the drug as they still possess this crucial DNA repair mechanism.

Professor Alan Ashworth, director of the Breakthrough Research Centre​ at The Institute of Cancer Research who led the research said: "This is a brand new therapeutic approach, centred on exploiting a specific deficiency in breast cancer cells - their Achilles' heel."​

"This is only possible because of our ever-increasing understanding of the basic molecular biology of cancer,"​ he added.

Most breast cancer patients are treated with drugs that kill tumour cells but also damage normal cells. It is damage to normal cells that can lead to distressing side effects, like nausea and hair loss. The advantage of this new approach is that it is targeted; tumour cells are killed while normal cells appear unaffected. This is because the new class of drugs, PARP inhibitors exploit the specific genetic make-up of some tumour cells.

Dr Andrew Tutt, a clinician scientist at the Breakthrough Research Centre and Breast Oncologist at Guy's Hospital, said: "This is a completely new approach in our fight against this type of cancer."​

"Targeted treatment holds considerable clinical promise. If our laboratory findings are confirmed in the clinic, we could dramatically improve the treatment of patients with BRCA1 or BRCA2 associated cancers,"​ he added.

The PARP inhibitors will enter Phase I trials within a few months, to monitor the safety of the drug and determine the most effective dose to take into larger clinical trials. If these trials are successful, these drugs will be ready for testing in clinical trials of patients with BRCA deficient tumours.

This new treatment might also be applicable to other forms of breast cancer that behave like BRCA deficient cancer. This group may represent more than 20 per cent of all breast cancers and is a key area of research in Professor Ashworth's laboratory.

The hormonal drug Tamoxifen has been the preferred choice in breast cancer treatment since the 70s. It has cut the death rate from breast cancer by reducing the recurrence of the disease in women who have had surgery and/or radiotherapy by 50 per cent. However the drug suffers from serious side effects that include an increased risk of blood clots, stroke and endometrial cancer.

The development of a new class of drugs called aromatase inhibitors in the past five years looks promising. Results from a trial of the first drug, called anastrozole showed it cut the recurrence of breast cancer in women who had already been treated for the disease by 76 per cent, with a lot less side-effects.