Our ability to probe deeply in the genome of normal and cancer cells continues to inform our understanding of the causes of breast cancer. While mutations in the well-known BRCA1 and BRCA2 genes confer the greatest breast cancer risk, these account for only 5-10 percent of breast cancers and only a fraction of familial (inherited) breast cancers.
Over 100 other genetic variants (altered DNA) have been identified as potentially increasing the risk of breast cancer. This has led to commercialization of multi-plex genomic panel tests of five to 20+ different genes. Dr. Ken Offit cautioned that interpreting the results from these tests is complicated by a lack of understanding of the significance of many of the newly identified variants. He described work his group is doing in collaboration with several BCRF investigators to gain a better understanding of some of the ambiguous genetic alterations and their significance in high-risk families, including a pilot study to increase genetic screening in a US Ashkenazi Jewish population.
Dr. Mary-Claire King updated the audience on recent findings from the New York and Middle East Breast Cancer Studies (NYBCS and MEBCS, respectively) in Ashkenazi populations. Results from the NYBCS further validate the CHEK2 gene as a breast cancer risk gene, although not in the same risk category as either BRCA1 or BRCA2. Based on studies from the MEBCS, Dr. King and her Middle East colleagues believe that population-wide screening in the Ashkenazi population could identify many more at-risk individuals then relying on family history as criteria for screening. A prevention trial is under way in young BRCA1 mutation carriers.