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Family history can trump breast cancer gene test

By LAURAN NEERGAARD, AP Medical Writer  Tuesday, November 18, 2008

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WASHINGTON -- If breast cancer runs in the family, women can be at high risk even if they test free of the disease's most common gene mutations, sobering new research shows.

The genes BRCA1 and BRCA2 are linked with particularly aggressive hereditary breast cancer and an increased risk of ovarian cancer, too. When a breast cancer patient is found to carry one of those gene mutations, her relatives tend to breathe a sigh of relief if they test gene-free.

But those headline-grabbing genes account for only about 15 percent of all breast cancer cases. Even in families riddled with breast cancer, a BRCA gene is the culprit only in roughly one family of every five that gets tested, said University of Toronto cancer specialist Dr. Steven Narod.

So clearly members of those families remain at risk from other yet-to-be-found genes, but how much risk?

Narod tracked nearly 1,500 women from 365 breast cancer-prone families, who tested negative for BRCA1 and BRCA2 mutations.

After five years, those women had a fourfold higher risk than average women of developing breast cancer, Narod reported Monday at a meeting of the American Association for Cancer Research.

This is crucial information for women considering gene testing, said Georgetown University genetics counselor Beth Peshkin, who wasn't part of the study.

"This is contrary to what I think the common perception is," Peshkin said. "Unless a mutation is identified in the family, a negative test result doesn't provide reassurance."

The good news: Narod's study showed these women didn't have an increased risk of ovarian cancer, like BRCA1- and BRCA2-carriers do.

While the $3,000 BRCA tests are well-accepted, newer tests for other genes linked to breast cancer are coming on the market.

But "the family history is a much stronger predictor," Narod stressed. He recommends that such women take the anti-cancer drug tamoxifen and undergo MRI cancer checkups instead of easier mammograms "regardless of what other gene tests showed."

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