Faulty genes linked to breast cancer

2 markers found in women with bad tumours Drugs developed for Alzheimer’s may help

Toronto scientists have discovered two genetic mutations that are linked to more aggressive breast cancer and a dramatically higher death rate in patients. A study of breast cancer tumours in 108 women found those that overproduce either one or both genes, called Notch 1 and Jagged 1, were far less likely to survive for five years. Women with tumours that overproduce both genes were even less likely to survive the disease, says the research published today in the journal Cancer Research.

“These two genes are likely markers indicating a patient’s probable prognosis,” said Dr. Michael Reedijk, a surgical oncologist at Princess Margaret Hospital. The two genes are part of a signalling pathway involved in breast cell division and communication. When they become overactive, they appear to be linked to aggressive tumours that occurred in about 25 per cent of the women.

While a larger study of 1,000 women needs to be done, the discovery is exciting because drugs have already been developed to inhibit these signalling pathways, Reedijk said. These drugs were created to block the pathways that lead to the buildup of amyloid plaques in the brains of Alzheimer’s patients.

“ We’re benefiting from 10 years of research that’s been done on generating drugs to treat Alzheimer’s disease,” he said.

Cancer patients wouldn’t be told they have these genetic markers because “ there is nothing we could do about it at this point,” Reedijk said. But if the findings hold up, scientists could develop a way of screening for the markers, which would help in determining how to treat them.

Reedijk estimates it could take five years to get a drug approved to inhibit the cancer genes. The discovery is the latest to find a genetic marker for breast cancer that can then be treated with a targeted drug that attacks the overactive gene but not the surrounding healthy tissue. Women with breast cancer whose genes produce the protein HER-2 can now cut their risk of having the cancer return by taking the targeted drug Herceptin.

While cancer is now known to be a disease of the genes, although most cancers are not inherited, few drugs have yet been developed to target those genetic mutations.

If the Toronto study holds up and the drugs already developed work against those genes, it would be a significant breakthrough.

Reedijk worked with Dr. Sean Egan, senior scientist at the Hospital for Sick Children, who first hypothesized that since the signalling pathway is important in the day-to-day function of breast tissue, abnormal pathways could lead to breast cancer.

“ It’s an early study but it’s potentially very exciting,” Reedijk said. Most of the cancer tissues studied came from the U. S. National Cancer Institute and were 10 years old, which made it possible to determine the patients’ outcomes, said Egan. The existence of drugs to treat these genetic mutations is an “exciting edge,” he said, “but these are all things to be done in the future. There still needs to be a number of things done.”