Lyndsay N. Harris, MD
Diana Hyland Chair in Breast Cancer
2012-2013 BCRF Project:
(made possible by generous support from ULTA Beauty)
Director, Breast Cancer Program
Professor of Medicine
Division of Hematology and Oncology
University Hospitals - Seidman Cancer Center
Case Western Reserve University School of Medicine
Defining markers of response to taxanes, Herceptin® (trastuzumab), and Avastin® (bevacizumab) based therapy is critical, as these agents are all used to treat breast cancer yet good biomarkers to predict who benefits most do not exist. Bevacizumab has been shown to be beneficial to early stage breast cancer in two exciting New England Journal of Medicine papers earlier this year. However, the toxicity of this agent cannot be under- estimated, and markers of response to therapy are critical to define.
Dr. Harris's work in the last year has discovered a new 6-gene signature that predicts complete response to trastuzumab. In addition, they have found that down-regulation of the TGF-b pathway is seen in all tumors that achieve a complete response to bevacizumab. They have previously found that luminal A tumors, a breast cancer subtype which is characterized by an excess of estrogen receptors, benefit most from weekly paclitaxel therapy. These discoveries are now being validated in further clinical trials, and the mechanisms studied in tumorspheres grown from the same patient.
Mid-year Progress: Dr. Harris's team continues to validate gene signatures in HER2-positive breast cancer based on samples collected from a small clinical trial involving 60 patients, which completed accrual in June 2012. The clinical data from this study is under preparation for an abstract to be presented at an upcoming meeting of the American Society of Clinical Oncology (ASCO).
The team is also continuing to analyze tissue samples collected from the HER2-negative arm of the BrUOG preoperative carboplatin/nab-paclitaxel (Ab) and bevacizumab (bev) clinical trial. Their presentation last June at ASCO Annual Meeting demonstrated differential expression of genes and pathways for each therapy and that bevacizumab-treated samples modulate pathways of angiogenesis including a tumor vasculature gene signature. However, they found that transcriptional changes in angiogenic pathways were not associated with pathologic complete response in this study. Therefore, Dr. Harris's team took a bottom-up approach to ask what pathways were involved in response to bevacizumab, using pCR as the endpoint. They are using several methods to evaluate the tissue samples, including protein analysis and DNA and RNA sequencing.
Dr. Harris's team is also conducting ex-vivo analysis of response to trastuzumab and bevacizumab. They have developed culture methods for mammospheres in the Harris laboratory using tissues remaining from mastectomies. The mammosphere samples will allow the research team to evaluate tumoral heterogeneity as it relates to drug response, as they can isolate individual mammospheres that should represent a clone of cells, and study the cells' evolution in the context of exposure to these therapies.
Dr. Lyndsay Harris is a nationally recognized expert in breast cancer treatment and research. She joined the faculty of Case Western Reserve University School of Medicine in March 2012. Formerly, she was an Associate Professor of Medicine, Medical Oncology, at the Yale School of Medicine. She had served as Head, Breast Medical Oncology, Smilow Breast Center and Co-Leader, Cancer Genetics and Genomics, Yale Cancer Center.
Dr. Harris has focused her research into the molecular classifications of breast cancer and the development of novel strategies to evaluate and treat breast cancer. She is the principal investigator for several phase I, II, and III clinical trials for the treatment of advanced breast cancer. Prior to joining Yale, Dr. Harris was an Assistant Professor at the Dana-Farber Cancer Institute and an Attending Physician at the Breast Oncology Disease Center at Dana-Farber. Dr. Harris has served leadership roles on several prominent national committees, including as the Associate Chair for Breast Cancer, American Society of Clinical Oncology Tumor Marker Guidelines Subcommittee, Alliance for Clinical Trials in Oncology (formerly Cancer and Leukemia Group B) Breast Committee Correlative Science Co-Chair, and a cadre member of the Department of Defense Integration Panel. Dr. Harris received both her undergraduate degree and medical degree from the University of Alberta. She fulfilled her internship requirements at the University of Alberta and served as a fellow in medical oncology at the University of British Columbia. Dr. Harris completed her postdoctoral fellowship at Georgetown University Medical Center.