Moderate breast cancer risk in women with negative gene tests

Women with a family history of breast cancer who do not have mutations in the breast cancer genes BRCA1 and BRCA2 are still at increased risk of developing the disease, say UK researchers. The scientists say that women who test negative for the mutation carried by their affected relatives still have three times the risk of women who have no family history, say the team, based at St Mary's Hospital in Manchester. The scientists say their results, published online in the journal of Medical Genetics, show that such women should be screened regularly from the age of 40 onwards.

Most breast and ovaran cancers are not inherited, but around 5-10 per cent are caused by inherited mutations - many of them in one of two genes, called BRCA1 and BRCA2. Previous studies of families with several affected members have shown that the lifetime risk for women who inherit a mutated BRCA1 or BRCA2 gene can be as high as 85 per cent. Such women also have an increased lifetime risk of ovarian cancer: 40-65 per cent for those with a BRCA1 mutation, and 20 per cent for those with a BRCA2 mutation.

In the latest study, the researchers assessed the families of 277 women in whom BRCA gene mutations had been identified. Of these, 190 had breast cancer, 48 had ovarian cancer and 33 had both, while six were free from the disease. Almost half of the 531 female relatives tested negative for the 'family mutation', but 28 of these women still developed breast cancer, whilst four developed ovarian cancer.

The scientists calculate that first degree relatives with negative BRCA ð test results have around three times the risk of developing breast cancer by the age of 50 as the general population. Team leader Professor Gareth Evans said that 'up until now when we have found a genetic fault in a family, we have assumed that if you do not have that fault, your risk of breast cancer is no different to anyone else'. However, he said the new findings show that 'here are far too many women in these families who test negative for the mutation but who develop breast cancer'.

Professor Evans said that because these women were in the 'moderate risk' category for breast cancer, they should be offered annual breast screening between the ages of 40-49, rather than being treated like the general population, in which screening usually begins at 50. He said that the increased risk was probably due to the women inheriting combinations of other genes that gave them a greater predisposition to breast cancer. 'We now know there may be 40 or 50 genes that increase breast cancer risk', he explained, adding 'even when you are in a high risk family with BRCA1 and BRCA2, you still have to take into account these other genetic factors that may be in those families'.