Mutations in the BRCA1 breast cancer gene appear to be linked with the loss of a protein important for putting the brakes on cell growth, a finding that could lead to new therapies, researchers said on yesterday.

The breakthrough could lead to more effective therapies for women with an aggressive and especially deadly cancer known as triple-negative that does not respond to current advanced drugs, the researchers said.

"It doesn't have a good target for therapy at this point," said Dr Ramon Parsons of Columbia University Medical Center in New York, who worked on the study.

Scientists have known for more than a decade that women with certain alterations in the BRCA1 gene were at high risk for breast cancer. What they have not understood is exactly how a mutation in this gene leads to cancer.

Researchers at Columbia, working with a team at Sweden's Lund University, now believe mutations in the BRCA1 gene can leave cells incapable of repairing routine DNA damage. When such damage occurs in a protein called PTEN, which regulates the growth of cells, cell growth is unchecked and tumors form.

Women with faulty copies of BRCA1 or BRCA2 have a 50 to 85 percent chance of getting breast cancer. Mutations in these genes account for 5 to 10 percent of breast cancer cases.

Most breast tumors are called estrogen-receptor positive, because they are fuelled by the hormone estrogen. About 20 percent are HER2-positive, because a protein called HER2 is involved.

A third type is driven by the hormone progesterone.

These types of cancer have good treatments.

Then there are basal-like or triple-negative tumors, so named because they lack estrogen, progesterone or HER2 receptors needed for most breast cancer drugs to work.

"The basic idea is that BRCA1 is a repair enzyme that is involved in coordinating the repair of double strand DNA breaks," said Parsons said.

"When it is mutated, it is no longer present in a cell. If a cut occurs in PTEN, there is no way for this cell to fix it," said Parsons, whose study was published in Nature Genetics.

(Agencies via China Daily December 10, 2007)