11/27/2013 11:11 am ET

Why Women Who Test Negative For BRCA Mutation May Still Face A Higher Breast Cancer Risk


Women who test negative for family-specific BRCA2 mutations, but whose family members possess the mutations, may still be at a higher risk for breast cancer, according to a new study.

Possessing a gene mutation in the BRCA1 or BRCA 2 genes is a known risk factor for breast cancer; researchers had previously believed that even if a woman had family members with mutations in one of these genes, if she tested negative for the mutation, her risk of breast cancer would then be equivalent to that of the general public.

But "we found that women who test negative for family-specific BRCA2 mutations have more than four times the risk for developing breast cancer than the general population," study researcher Gareth R. Evans, M.B.B.S., M.D., M.R.C.P., F.R.C.P., an honorary professor of medical genetics and cancer epidemiology at the Manchester Academic Health Science Center at the University of Manchester, said in a statement. "We also found that any increased risk for breast cancer is largely limited to BRCA2 families with strong family history and other genetic factors."

The findings, published in the journal Cancer Epidemiology, Biomarkers & Prevention, included data from 807 families with BRCA mutations who were in the M6-Inherited Cancer in England Study. Among these families, 49 women were identified who developed breast cancer despite testing negative for the family-specific BRCA mutation; 22 of the women tested negative from BRCA1 families, while 27 tested negative from BRCA2 families.

Researchers grouped these women based on age into four groups -- 30 to 39, 40 to 49, 50 to 59 and 69 to 80 -- and found that there were twice as many cases of breast cancer among these women who tested negative for the family-specific BRCA mutation, compared with the general population.

Then, to calculate the risk of breast cancer of these women compared with those of the general population, researchers calculated the "observed versus expected ratio" (in other words, the ratio of risk for women who tested negative for BRCA but whose families had BRCA mutations, compared with the ratio of risk for women in the general population).

They found that the overall risk of breast cancer was not actually much higher among women who came from families with the BRCA1 mutation. However, the risk was fourfold higher for women who came from families with the BRCA2 mutation.