Negative BRCA Test Did Not Mean Lower Breast Cancer Risk

Breast cancer risks were higher in women who tested negative for family BRCA2 mutation

/ Author:  / Reviewed by: Joseph V. Madia, MD Beth Bolt, RPh

(RxWiki News) If a woman’s close relative is known to carry a BRCA gene mutation, she will want to see if she is also a carrier. If this woman learned that she didn’t have an altered BRCA gene, that might offer some relief.

However, a recent study suggested that the absence of a BRCA gene mutation doesn't necessarily mean a woman is without risk.

Mutations in the BRCA1 or BRCA2 gene increase a woman’s lifetime risk of breast cancer and ovarian cancer.

Researchers in England have found that women who tested negative for family-related BRCA2 gene mutations were still at higher risk of breast cancer than women with no family history of the disease.

"Determine your individual breast cancer risk."

Gareth R. Evans, MBBS, MD, honorary professor of medical genetics and cancer epidemiology at the Manchester Academic Health Science Center at the University of Manchester in the United Kingdom, led a team of researchers who evaluated the breast cancer risks of women who tested negative for family-specific BRCA mutations.

These researchers used data from the M6-Inherited Cancer in England study, which has been conducting family BRCA screenings since 1997.

A total of 809 families were found to have members who carried either a BRCA1 or BRCA2 genetic mutation.

Among these families, breast cancer was diagnosed in 49 women who were tested and found not to carry the family-specific BRCA mutation.

“Although testing negative for a family-specific mutation, it appears that some women may still be at increased risk of breast cancer if there are multiple members of the family with mutation-related breast cancer, particularly if they were detected at young ages,” the researchers wrote.

The number of breast cancer cases among the non-carriers of family-related BRCA1 was about the same as would be expected in the general population, according to the researchers.

However, among non-carriers of family-specific BRCA2 genes, the number of breast cancers was 4.57 times higher than what would be seen in women with no history of breast cancer.

When the timing of testing both the original family member and the non-carrier were considered, this risk dropped from 4.57 to 2.01, which is still double the risk expected.

Dr. Evans said in a statement, "It is likely that these women inherit genetic factors other than BRCA-related genes that increase their breast cancer risk."

"This is very interesting work and suggests that there may be other genes which modify the effects of BRCA1 and BRCA2," Adam Brufsky, MD, PhD, professor of medicine at the University of Pittsburgh, told dailyRx News. "Presence of alleles [alternative forms of genes] of these potential 'BRCA modifying' genes may in and of themselves increase the risk of breast cancer without mutations in BRCA1 or BRCA2."

As a result of these findings, the authors of this study noted that specialists should be cautious when describing the breast cancer risks of women who test negative for family-related BRCA2 genetic mutations, particularly if there’s a strong family history of the disease.

This study was published November 27 in Cancer Epidemiology, Biomarkers & Prevention, a publication of the American Association for Cancer Research.

The National Institutes of Health funded this study.

No conflicts of interest were disclosed.

Review Date: 
November 26, 2013
Last Updated:
December 30, 2013