Charles M. Perou, PhD, May Goldman Shaw Distinguished Professor of Molecular Oncology, professor of Genetics, and Pathology and Laboratory Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, discusses the biomarker assay results as described in the ASCO breast cancer guideline.

Prior to publishing the recommendations, ASCO examined various gene expression tests to determine how they should be used for patients based on their intrinsic subtype, Perou explains. The guideline also provides the level of evidence for each test. This is helpful for practitioners, he adds, as several tests are similar but have varying levels of evidence.

For one of the tests, the PAM50 risk of recurrence score—which Perou helped develop&mdash;ASCO determined that this test had a good level of evidence to be used to make adjuvant systemic therapy decisions in the node-negative setting for patients with estrogen receptor/progesterone receptor-positive, HER2-negative breast cancer.

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Charles Perou on Biomarker Assay Use in ASCO Breast Cancer Guideline

Charles M. Perou, PhD, professor of genetics, pathology & laboratory medicine, UNC Lineberger Comprehensive Cancer Center, discusses a trial (CALGB 40601) presented at the 2014 ASCO Annual Meeting that analyzed gene expression signatures in patients with HER2-positive breast cancer treated with weekly paclitaxel and trastuzumab with or without lapatinib.

This trial demonstrated that dual HER2-targeting improved pathologic complete response (pCR) by about 10%, though this was not statistically significant. Even so, Perou says there were biologically interesting trends observed in this analysis.

RNA analysis was performed to do gene expression profiling and evaluate genomic signatures as potential predictors of pCR and/or response to adding lapatinib to trastuzumab. The overall interesting finding here, Perou says, was that there were a number of different genomic signatures that were predictors of an increased likelihood of having a pCR. It was also discovered that the HER2-enriched subtype had high pCR rates (about 70%) in the paclitaxel/trastuzumab arm and almost 80% in the dual HER2-targeting arm. The pCR rate in all other subtypes was about 30-40%, Perou says.

Charles M. Perou, PhD, discusses a trial (CALGB 40601) presented at the 2014 ASCO Annual Meeting that analyzed gene expression signatures in patients with HER2-positive breast cancer treated with weekly paclitaxel and trastuzumab with or without lapatinib.

Charles M. Perou, PhD, Discusses Genomic Signatures and Dual HER2-Targeting in Breast Cancer

Charles M. Perou, PhD, professor of genetics, pathology & laboratory medicine, UNC Lineberger Comprehensive Cancer Center, discusses the next generation of sequencing technology and tests for breast cancer.

The clinical application of new sequencing tests hinges upon ongoing clinical trials. Perou describes that conventional trials must first validate the efficacy of new agents, which must be conducted alongside biomarker studies looking at a handful of driver mutations or whole genome sequencing. The goal of these trials is to establish whether specific mutations can predict a response to therapy.

Trials are currently investigating therapeutics that inhibits phosphoinositide 3-kinase (PI3K) activity. A mutation in PI3K occurs in approximately 30-40% of all breast cancer. There are currently multiple PI3K inhibitors in clinical development, but it is still unclear whether having the mutation makes you more sensitive to therapy. Additionally, other markers, such as PTEN, which is downstream from PI3K, could be implicated in the effectiveness of treatment.

Perou notes that research is on the right track, but the clinical application of these new agents may still be multiple years down the road.

Dr. Charles Perou, from the UNC Lineberger Comprehensive Cancer Center, on Next Generation Sequencing Technology

Charles M. Perou, PhD

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Charles Perou on Biomarker Assay Use in ASCO Breast Cancer Guideline

Charles M. Perou, PhD, Discusses Genomic Signatures and Dual HER2-Targeting in Breast Cancer

Dr. Perou on Next Generation Sequencing Technology