Lyndsay N. Harris, MD
Diana Hyland Chair in Breast Cancer
Director, Breast Cancer Program
Professor of Medicine
Division of Hematology and Oncology
University Hospitals - Seidman Cancer Center
Case Western Reserve University School of Medicine
2013-2014 BCRF Project:
(The ULTA Beauty Award)
Defining biomarkers of response to taxanes, trastuzumab and bevacizumab-based therapy is critical as these agents are all used to treat breast cancer yet good biomarkers do not exist. If doctors knew before prescribing a medication which patients would benefit from a particular treatment they could use that specific drug, whereas if a patient is not likely to benefit from, trastuzumab for example, they may have more benefit from a drug like pertuzumab or TDM1. Even bevacizumab (Avastin), which recently lost FDA approval, has been shown to be beneficial to early stage breast cancer in two exciting New England Journal of Medicine papers last year. However, the toxicity of this agent cannot be underestimated, and markers of response to therapy are critical to define. Dr. Harris’s work in the last year has discovered a new signature that predicts complete response to trastuzumab. In addition, she has found that downregulation of the TGF-b pathway is seen in all tumors that achieve a complete response to bevacizumab. Her team has further evaluated the genetic mutations that occur in these tumors and has seen that particular mutations in genes like p53 may be lost during treatment and that this is associated with a good response to therapy. Dr. Harris’s goal is to integrate the findings of these genomic studies to provide the best predictor of benefit from therapy for early stage and advanced breast cancer using genomics.
In addition to doing genomic testing on the tumors from biopsies that were so graciously donated by patients, Dr. Harris’s group is trying to grow the cells from these tumors so they can see how they behave in culture. They have successfully grown “mammospheres” from patient tumors and are now developing the methods to grow them with the same patients “stroma” (the other cells in the breast that support breast cells to grow). It has been shown in several studies that breast cells and tumors like to grow in their own stroma. It is also know that the fibroblasts (part of the stroma) that are associated with cancer cells promote tumor growth, these cells are known as cancer-associated fibroblasts (CAFs). Dr. Harris has successfully grown CAFs in culture this year and is now mixing them with tumors from the same patient. Her goal for this aim of the grant is to develop “co-culture” conditions that best mimic the natural environment of the tumor and study the mechanisms of resistance to trastuzumab, bevacizumab and chemotherapy in that setting.
Dr. Harris’s work continues to refine biomarkers that determine which patient will benefit from therapy after only one dose of biologic treatment (either trastuzumab or bevacizumab). Her team has discovered several that are promising: IGF-1, AKT, stem cell signature in HER2 positive and a TGFb signature in HER2 negative. Ongoing studies are designed to validate these findings in prospective clinical trials and to understand the mechanism of these changes by studying tumor mutations and developing models to study these findings outside the body. In addition to doing genomic testing on the tumors from biopsies that were so graciously donated by patients, they are trying to grow the cells from these tumors so we can see how they behave in culture. Their goal here is to develop ‘co-culture’ conditions that best mimic the natural environment of the tumor and study the mechanisms of resistance to trastuzumab, bevacizumab and chemotherapy in that setting. The overarching goal is to develop an ‘early triage’ of the right patient to the right targeted therapy and ultimately improve both cure rates and reduce unneeded toxicity from treatment.
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.