Canadian researchers have said that women, with a family history of breast cancer, who test negative for two genetic mutations commonly linked to breast cancer, could still be at a high risk of developing the disease. The genes in question are BRCA1 and BRCA2, which are linked with particularly aggressive hereditary breast cancer and an increased risk of ovarian cancer as well.

According to researchers led by Dr. Steven Narod of the University of Toronto, these women were four times more likely to develop breast cancer as compared to an average woman which added up to a 40 % lifetime risk of getting the disease. Narod said, "I think we were surprised that it was that high. But certainly at that level of risk, one would think about preventive measures."

In the study researchers tracked 1,500 Canadian women from 365 breast cancer-prone families and an average of 48 tested negative for BRCA1 and BRCA2 mutations. All the women came from families with a history of breast cancer where either two or more cases of breast cancer among close relatives under age 50 or at least three cases among close relatives of any age were seen.  After a five year study they were found to have a fourfold higher risk of developing the disease. Narod said the lifetime risk of breast cancer estimated for these women compared to the roughly 80 % lifetime risk for women with the BRCA1 or BRCA2 mutations.

Georgetown University genetics counselor Beth Peshkin, who wasn't part of the study said, "This is contrary to what I think the common perception is. Unless a mutation is identified in the family, a negative test result doesn't provide reassurance."

The silver lining in the dark cloud was that these women did not have an increased risk of ovarian cancer, like BRCA1- and BRCA2-carriers do. Narod said the women may want to consider the drug tamoxifen as a preventive measure and include magnetic resonance imaging, or MRI, exams of the breast which are considered a more sensitive screening test for breast tumors than a mammogram,

According to the American Cancer Society breast cancer kills about 465,000 women worldwide and 1.3 million develop it every year. Women with an Ashkenazi, or Eastern European, Jewish background have a higher likelihood that a woman's breast cancer is linked to the BRCA1 and BRCA2 genes.

Narod stressed that the family history is a much stronger predictor," and regular MRI’s were needed "regardless of what other gene tests showed."

The study results were presented at a meeting of the American Association for Cancer Research.