Sequencing of Breast Cancer Tumors Predict Clinical Restults Following Single Dose Therapy

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New research from University Hospitals (UH) Case Medical Center Seidman Cancer Center and Case Comprehensive Cancer Center at Case Western Reserve University analyzed how changes in the genetic composition of breast cancer tumors following brief exposure to either biologic therapy or chemotherapy can foretell future clinical outcomes in patients.

Results demonstrated that through deep genome sequencing, a reduction in the most frequently mutated genes in breast cancer could be observed after just one dose of preoperative therapy. Deep sequencing is a process that involves sequencing the same region several times to distinguish mutations within tumors that hold significance in cancer evolution. The team’s findings were presented during the 2013 San Antonio Breast Cancer Symposium.

"Genomics is the new frontier of cancer research, and this study shows that we may be able to accurately determine what treatment methods will and will not be effective for individual patients after just one dose of medicine. The ability to understand potential clinical outcomes for patients earlier in the treatment process would provide physicians with better opportunity to personalize patients' medicines according to their own tumor responses,” said study investigator and Director, Breast Cancer Program, UH Seidman Cancer Center and Professor of Medicine at Case Western Reserve University School of Medicine, Lyndsay Harris, MD.deep squence

Over 209,000 patients in the U.S. are diagnosed with breast cancer every year. The projected outcome of studying the genetic makeup of breast cancer patients is to decide who will benefit most from certain drug therapies and to apply that information to create a personalized treatment plan for each patient involved.

Researchers assessed 120 Stage IIA to IIIB breast cancer patients and compared a first biopsy after brief exposure to either biologic or chemotherapy treatment with a second biopsy taken after surgery.

Researchers employed deep genomic sequencing to quantify the abundance of clonal mutations in breast core biopsies, evaluate changes in these mutations following brief exposure to a targeted therapy and then assess the consequent change in abundance of these mutations following exposure.

This process of quantifying and observing clonal mutations between preliminary therapy exposure and surgery enabled researchers to find out how changes in the abundance of these mutations related to a patient's response to preoperative therapy. Through this analysis, the researchers concluded that clonal abundance upon brief exposure to therapy may be linked with clinical outcomes.

Harris and her team are currently incorporating whole genome profiles with deep sequencing data as they lead a new study at UH Seidman Cancer Center to verify these preliminary findings presented in San Antonio.