A patient with a strong family history of breast and ovarian cancer wanted to know if there was any advantage to doing the broader panel vs. just BRCA 1/2. Her family history was notable for breast cancer in her mother at age 52 and an aunt with ovarian cancer at age 47. The family history was also notable for a maternal uncle with colon cancer and her maternal grandfather had Non-Hodgkins Lymphoma. Unfortunately, her insurance had a very high deductible and she was going to pay out of pocket. The BRCA 1/2 test alone can be done for $1500 but the multi-gene panels are much more expensive depending on the laboratory and the additional tests involved.
To answer this question we refer to a recent article published in the Annals of Surgical Oncology form July 2015. In the olden days prior to new methodology of next generation sequencing the strategy would always be to test sequentially. In this case, that would be doing BRCA 1/2 first and if negative then move to the other genes that are less penetrant but confer an increased risk for breast/ovarian cancer.
In this study, they took patients that had undergone only BRCA 1/2 testing and then did further multi-gene panel testing. The detection of BRCA 1/2 mutations were the same as would be expected because next-generation sequencing should also identify BRCA mutations. However, approximately 4% of women were found to have non-BRCA mutations that were considered pathogenic or contributing to disease. Most improtantly, almost 14% of women were identified to have Variants of Unknown Significance (VUS) in non-BRCA genes.
VUS usually require more interpretation in light of the family history but in cases where there is a strong family cancer history, many of them can be interpreted to be significant and contributing to breast / ovarian cancer risk and other cancer risk in that family and individual.
So what is our Testing Strategy: