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Evolution of Genetic Testing in Breast Cancer Continues

Angelica Welch
Published: Thursday, Jun 21, 2018

Michael Simon, MD, MPH
Michael Simon, MD, MPH
Genetic testing in breast cancer has advanced rapidly over the last decade, offering therapeutic options and providing early screening opportunities, says Michael Simon, MD, MPH. In a presentation during the 2018 OncLive® State of the Science Summit™ on Breast Cancer, Simon, a medical oncologist at Karmanos Cancer Institute, discussed advances in genetic testing for breast cancer, highlighting the overlap between genomic risk assessment and tumor genomic profiling.

as well as for panels of other genes, said Simon. This led to next-generation sequencing (NGS), which allows researchers to process millions of genes simultaneously. NGS generates large amounts of data, which allows researchers to make genotype to phenotype correlations.

Identifiable Genes

About 50% of variants that predispose patients to breast cancer are known—15% of genes are BRCA1/2; 14% are known singlenucleotide polymorphisms (SNPs); 14% are other predicted SNPs; 4% are CHEK2, ATM, PALB2, BRIP1, RAD51C, RAD51D, and BARD1; and 3% are TP53, PTEN, LKB1, and CDH2. The remaining 50% are unexplained, says Simon.1

The variant that occurs third most often, P53, is associated with Li–Fraumeni syndrome, which is known to signify a very high risk of early onset cancer.

Genetic Tests and Their Limitations

Testing methods for these genes include multiplex panel assays and cascade testing. Additionally, there are therapeutic implications if a mutation is discovered in a patient’s breast cancer, such as treatment with PARP inhibitors that are specifically used in patients with BRCA1/2 mutations.

Some of the limitations are the variants of uncertain significance (VUS), incidental surprise results, uncertain recommendations, and inconsistent results.

“We have approximately 20,000 genes, and each gene is like a book, telling a different aspect of our body,” explained Simon. “[VUS] are changing in the gene where there is an unknown association with cancer risk. These come in different flavors, as well.”

VUS are likely pathogenic, Simon said, and if a patient comes in and has a result disclosing a VUS, the laboratory will eventually be able to reclassify the change. But outright, it is uncertain.

However, a surprise result would be the appearance of the CDH1 mutation on the panel test, he said. CDH1 is associated with hereditary gastric cancer.

“Whenever I see a family and talk about panel testing, I warn them about that possibility,” Simon said. “When women are coming in for genetic breast cancer panel testing, they aren’t thinking that they will come out of that with an increased risk of gastric cancer, which is up to 83%. There is also risk of lobular breast cancer [with CDH1].”

Uncertain recommendations would occur in a situation where a patient displays a variant that does not have evidence-based data to suggest a course of action. Inconsistent results would be categorized as an instance wherein labs report differing results, which lead to no definite course of action.


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View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Advances In™ Tumor Testing: Interpreting Genomic Profiles to Optimize Breast Cancer TreatmentJun 29, 20191.5
Oncology Briefings™: Current Perspectives on Preventing and Managing Tumor Lysis SyndromeJun 30, 20191.0
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