BRCA Mutations May Cause Drug Resistance in Breast and Ovarian Cancer

There is a relationship between the genetics of BRCA1 and BRCA2 mutations and the risk of a patient with breast or ovarian cancer being resistant to platinum-based chemotherapy, according to recent research conducted at the Perelman School of Medicine at the University of Pennsylvania. The study’s senior author Katherine Nathanson, M.D., spoke with CURE about these findings.
BY DANIELLE BUCCO
PUBLISHED: SEPTEMBER 04, 2017
Katherine Nathanson, MD
Katherine Nathanson, M.D.
There is a relationship between the genetics of BRCA 1 and BRCA 2 mutations and the risk of a patient with breast or ovarian cancer being resistant to platinum-based chemotherapy, according to recent research conducted at the Perelman School of Medicine at the University of Pennsylvania.

The study’s senior author Katherine Nathanson, M.D., spoke with CURE about these findings.

The investigators evaluated the genetic profiles of 160 breast and ovarian cancers associated with germline mutations in BRCA1 and BRCA2. Historically, it had been thought that all BRCA1- and BRCA2-associated tumors lose the second genetic allele; however, the findings showed that this was not true.

In an interview, Nathanson, a deputy director of the Abramson Cancer Center, and director of Genetics at Basser Center for BRCA, University of Pennsylvania, discussed how the genetics of BRCA1/2-associated tumors impacts tumor development and response to treatment.

Can you provide an overview of this research?

We looked at breast and ovarian cancers, first using the data from The Cancer Genome Atlas (TCGA) and then using our local data from the University of Pennsylvania. These were all breast and ovarian cancers, specifically from patients who carried BRCA1 and BRCA2 mutations. 

The goal of the research was to characterize tumors from women who have BRCA1 and BRCA2 mutations. Although that had been done on the small scale, it hadn’t yet been done on a very large scale. We ended up investigating a total of 160 tumors associated with BRCA1 and BRCA2 mutations, with 100 from TCGA and 60 that were looked at locally at the University of Pennsylvania. Of those, we looked at 94 ovarian cancers and 76 breast cancers. 

The dogma had been that all BRCA1- and BRCA2-associated breast and ovarian cancers lost the second allele or the wild-type allele. We were somewhat surprised to find that they didn’t all lose the second allele. It was much more striking for BRCA2-associated tumors than for tumors associated with BRCA1

For BRCA1 mutations, most of them lost the second allele, but some did not. However, for BRCA2, a substantial proportion did not lose the second allele or the wild-type allele. 



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