Negative BRCA Test May Not Mean Lower Risk


If a woman has family members with BRCA2 mutations, but she tests negative for them herself, she may feel that she is free and clear from any excess risk for breast cancer.  However, scientists say this may not be true.  These women may still be at greater risk for developing breast cancer than the general population, they say.

The researchers say that women who have mutations in either their BRCA1 or BRCA2 genes are at greater risk for developing breast cancer.  While it has generally been assumed that testing negative for these mutations means that a woman only has the same degree of risk as anyone else, their study indicates that they may in fact still have an elevated risk for the disease if a relative possesses these mutations.

According to Gareth R. Evans, an honorary professor of medical genetics and cancer epidemiology at the Manchester Academic Health Science Center at the University of Manchester in the United Kingdom, his research team found that women who test negative for the BRCA2 mutation still have more than four times the risk for breast cancer.  In addition, they found that this increased risk  seemed to be limited to women whose families had this specific gene mutation.

Evans says he believes that it is likely that women inherit other genes, besides the BRCA genes, which also increase their risk for developing breast cancer.  There are about 77 single nucleotide polymorphisms (SNPs) which are linked to breast cancer, he says.  SNPs are genetic variations that help scientists track disease-carrying genes within families.  It may be necessary to identify more SNPs in order to understand why some women are at higher risk despite the fact that they don’t carry the BRCA gene.

In the study, Evans and his team took data from M6-Inherited Cancer in England, a study which has conducted breast and ovarian cancer screenings for BRCA1 and BRCA2 mutations since 1996.  Information from this study was then entered into a Filemaker Pro-7 database.  Out of 807 families with the BRCA mutations, there were 49 women who tested negative for the genetic mutations, but then proceeded to develop breast cancer anyway.  The team identified these women as being “phenocopies,” meaning that they exhibited the same traits even though they did not possess the same genes.

Out of the 49 women who were phenocopies, 22 were from BRCA1 families but tested negative for the gene.  In addition, 27 were from BRCA2 families, but tested negative.

When the researchers examined the women based upon age groups, they found that there were about two times more cases of breast cancer in each group than would be expected.

However, when they compared the number of breast cancer cases to what might be expected in the general population, they found that the number of cancer cases among those women coming from BRCA1 families was not significantly different.  But, among the women coming from BRCA2 families, their risk was much greater than what would be expected.  In fact, it was four times higher.

The research team states that cancer care providers should be very careful about telling women that they have no additional risk for cancer when they test negative for the BRCA2 gene because it may not be true if the woman’s family has a strong history with the gene.

The study was published on November 27, 2013 in the journal Cancer Epidemiology, Biomarkers & Prevention.

By Nancy Schimelpfening


Negative BRCA Testing May Not Always Imply Lowered Breast Cancer Risk – EurekaAlert!

Breast Cancer Risk in American Women – National Cancer Institute

 Phenocopies – Springer Reference

You must be logged in to post a comment Login