Researchers say they have discovered a major reason why women who inherit a mutated version of the gene BRCA1 run a high risk of breast cancer — and that finding might aid the search for new treatments.
A second gene, called PTEN, plays a key role, scientists said in a study released Sunday.
Scientists have long known that BRCA1 normally repairs damage to other genes. So if it is crippled by mutations, the unrepaired damage could be expected to lead to cancer. But the specifics of that story have been murky.
The new study fingers PTEN, which normally acts as a brake on cancer. The researchers found evidence that in breast cancers associated with a BRCA1 mutation, PTEN is often broken and does not get repaired. That sets off a chemical cascade that leads to malignancy.
This is "probably a major way" that defects in BRCA1 can produce breast cancer, said Dr. Ramon Parsons of Columbia University, who reports the work with colleagues on the Web site of Nature Genetics.
PTEN was discovered about 10 years ago, and scientists know a lot about it and the chemical pathway that gets activated when PTEN is disabled, he said. Drug companies have been testing drugs in animals that seek to treat tumors by interrupting that cascade, and they have gotten some encouraging results, he said.
Breast cancers associated with the BRCA1 gene are generally aggressive and have a poor prognosis. BRCA1 and its cousin BRCA2 account for less than 15 percent of all breast cancers.