BOSTON (The Boston Globe) -- Boston researchers Thursday announced the discovery of six genetic markers for breast cancer risk, potentially enabling thousands of women with the genetic mutations to protect themselves against breast tumors before they develop.

The finding remains preliminary, and will require an extensive population study before the gene mutations can be decisively linked to cancer. However, researchers hope the mutations could explain thousands of US breast cancer cases that develop each year. If confirmed, the new markers would also allow doctors to expand screening for breast cancer risks beyond the two well-known "breast cancer gene" markers that have so far been identified.

"Now testing for mutations in these other six genes might become a routine part of gauging breast cancer risk," said Harvard Medical School pediatrics professor Dr. Alan D'Andrea, who led the research effort. The results were published Thursday on the Internet edition of the journal Science.

Women testing positive could consider lifestyle changes, such as diet and exercise programs, and frequent screening for early signs of cancer. They may also consider preventive drug therapies or even breast and ovary removal surgery, all of which have varying levels of success in preventing cancer onset.

These hard choices are already faced by the 2 in 1,000 American women with the BRCA1 and BRCA2 gene mutations, the prime culprits in inherited breast cancer. Although the cause of most breast cancers is still unknown, up to 10 percent of the 180,000 breast cancers in the United States each year are inherited, and 75 percent of those inherited cancers feature one or both BRCA mutations. But the six new genetic markers - DNA mutations that hamper a cell's ability to repair itself - could explain some portion of the remaining 25 percent of inherited cases, as well as many other unexplained cases. Women with family histories of breast cancer could soon be tested for the six new genetic markers in addition to the two BRCA mutations, said specialists.

For the moment, the prevalence of the six new mutations in the population remains unknown, as does the risk it confers on those who carry it.

The six genes from the new research appear intimately linked with the two BRCA genes. BRCA genes, short for breast cancer genes, fix DNA errors in cells. Mutations hamper their repair abilities, allowing errors to proliferate, which can turn cells cancerous. Women with mutated BRCA genes face a 59 to 85 percent lifetime breast cancer risk, and a 15 to 65 percent ovarian cancer risk, both far higher than the general population.

The six newly identified genes, when functioning properly, activate the BRCA genes as needed, the researchers said. Together with the two BRCA genes, the eight genes form a genetic pathway - a cascade of DNA-driven events - crucial to cell health. So when one of the six new genes is damaged, even intact BRCA might not be able to perfom its task.

"You can think of the pathway as a fancy billiard shot," said D'Andrea. "Just as each billiard ball must strike the next one at the right speed and angle, each gene in the pathway must be activated in the proper sequence. A problem anywhere along the line can stymie the entire process."

To test this theory, the subject of much recent speculation among some molecular biologists, researchers at the Dana Farber Cancer Institute and Children's Hospital examined children with a rare blood disorder called Fanconi anemia. There are about 500 known US cases of the disease, usually caused by defects in the same six genes. These children develop bone marrow failure, depriving them of the ability to make red blood cells. Those that survive childhood face high lifetime cancer risks.

D'Andrea and his team examined five Fanconi anemia patients that strangely had no problems with those six genes. They found that each of those patients had BRCA2 mutations, meaning the defect behind many breast cancers was also causing the anemia.

Oregon Health Sciences University genetics professor Markus Grompe, who coauthored the new paper, said the next step would be to test breast cancer-afflicted families without BRCA mutations. If the six new mutations turn up frequently, then the link would be more definitively established, he said.

It is too soon to say how much the new genetic markers will effect oncologists' daily dealings with patients. Several cancer clinicians refused to speculate until further evidence is gathered.

But Dr. John Erban, oncology chief at Tufts-New England Medical Center, said it would likely lead to more aggressive breast cancer screening for women with family histories but not necessarily to more radical procedures like prophylactic breast removal.

"Until you have a really clear idea of how having these markers modifies the risk, that intervention is premature," he said.

D'Andrea said the six new gene mutations could also prove ripe targets for new drugs.

"Drug companies are going to lunge for this," he said.

Recent studies underscore the importance of early discovery of breast cancer predisposition. An international study of women with BRCA mutations released last month found that salpingo-oophorectomies - surgical removal of the ovaries and fallopian tubes before cancer occurs - cut breast cancer risk by 53 percent and ovarian cancer risk by 96 percent over seven years. Surgical removal of both breasts has been shown to reduce breast cancer risk by up to 90 percent.

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