Breast cancer breakthrough excites scientists

A drug that can destroy tumours with minimal side-effects could offer a breakthrough in the treatment of breast cancer.

A drug that can destroy tumours with minimal side-effects could offer a breakthrough in the treatment of breast cancer.

Tests on animals have shown the drug prevents the growth of tumours so effectively that clinical trials on humans will start within months, scientists said yesterday.

The drug is called a PARP inhibitor and is targeted to work against tumours caused by the inherited forms of breast cancer which result from mutations in the BRCA1 and BRCA2 genes.

Women carrying mutations in either of those genes have up to an 85 per cent chance of developing breast cancer by the age of 70. There is no specific treatment other than a prophylactic mastectomy.

Nearly 41,000 British 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.

However, the new drug might also be effective against other non-hereditary forms of breast cancer and could end up helping as many as 20 per cent of breast cancer patients, said Professor Alan Ashworth, director of the Breakthrough Research Centre at the Institute of Cancer Research in London.

"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," Professor Ashworth said.

Mutations in the breast cancer genes cause cells to proliferate uncontrollably and cause a tumour. The new drug induces another change in these cells that prevents them from repairing any further damage to their DNA, causing chromosomes to fall apart and the cancer cells to die.

"It's analogous to removing two legs of a table. Removing one leg is damaging but removing two causes the table to fall over. That is what the drug does to the tumour cell," Professor Ashworth said.

Most patients with breast cancer are treated with drugs that destroy cancer cells but can also damage healthy cells - it can lead to distressing side effects, such as nausea and loss of hair.

Professor Ashworth said the study on laboratory mice, published in the journal Nature, indicates the PARP drug is highly selective and appears to destroy cancer cells only, leaving healthy cells untouched.

"We've made this added leap. We've got a drug that works effectively and it's going into patients very soon. It real progress and has caused extreme excitement," he said.

Breast tumours in women who inherit mutations in either of the two BRCA genes occur because the cancer cells have lost a specific mechanism that can repair damage to DNA.

PARP inhibitors selectively kill cells where that form of DNA repair is absent and so are highly effective at destroying cancer cells but leave ordinary cells unharmed because they still have the vital mechanism for DNA repair.

In laboratory mice with implanted tumour cells, none went on to develop cancer after treatment with PARP and yet up to 80 per cent of the other "control" mice that had no treatment developed tumours.

Andrew Tutt, an oncologist at Guy's Hospital in London and a member of the research team, said: "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 and BRCA2 associated cancers.."

The drug was the result of 10 years of research by scientists working for Kudos, a pharmaceuticals company based in Cambridge. Professor Steve Jackson, the chief scientist at Kudos, said: "This discovery could well be the tip of the iceberg, as the technology behind it has the potential to treat a range of other cancers."

The research was jointly funded between the medical charities Breakthrough Breast Cancer, Cancer Research UK, the Wellcome Trust and the Mary-Jean Mitchell Green Foundation.

Case Study: Joan Nicholson, charity consultant

Joan Nicholson, a charity consultant from Middlesex and carrier of the BRCA2 gene, had a full oophorectomy (mastectomy and reconstruction) two years ago and a hysterectomy six months ago, as preventative measures to protect her from developing cancer.

"The cancer that runs in my family is a very aggressive form. Seeing members of my family going through chemotherapy, I felt I needed to do something to protect myself and I didn't feel there was anything out there other than having the surgery.

"I was given the option of having cancer tests, but with this strain, once you've found the cancer it is too late. The worst thing about the surgery was actually what people said about having my ovaries removed - that I would get night sweats and depression. Luckily I haven't had any of those symptoms.

"I am very worried about the girls in my family. There are a couple who do have the gene and others who haven't been tested. If I was younger and in a position to try the new treatment, it could make a big difference, even if the drug could just buy some time for sufferers or carriers of this gene.

"Some women I know had testing and know they carry the gene but are going to go ahead and take their chances. It is a very hard decision to make.

"There are a lot of different kinds of cancer but for BRCA1 and BRCA2 carriers, this could make a big difference."

Alex Valk

Past drugs

The hormonal drug Tamoxifen has been the gold standard 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, side effects 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 has persuaded many doctors they found a breakthrough. Results from a trial of the first drug, called anastrozoleshowed 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.

Jeremy Laurance