Lyndsay N. Harris, MD

In the post-genomic era, the time is now to define individual variability in tumor phenotype and host response in the context of treatment for breast cancer. This year, Dr. Harris and colleagues will take three approaches to the evaluation of markers which predict whether a specific patient will benefit from a particular therapy. They will apply these methods to two agents which are widely used for the treatment of breast cancer patients: trastuzumab (Herceptin®) and paclitaxel (Taxol®).

However, the approach can be applied to other agents. Such strategies are critical as the number of available drugs increases and the demand for personalized therapy becomes a priority. This proposal builds on earlier work supported by BCRF on cohorts of patients treated with trastuzumab and paclitaxel, to define markers of response to these therapies. In addition, the researchers have added a second dimension, that of host response to these agents. They will then attempt to integrate these data in a model which integrates tumor and host features of therapeutic benefit.

Mid-year Progress Report:
This project is designed to better understand the mechanisms of response and resistance to some of the most commonly used agents for breast cancer, paclitaxel and trastuzumab. Dr. Harris and team have developed techniques to perform genome-wide profiling from archived tissue for patterns of gene expression, DNA amplifications and deletions and multiplex protein markers. They have performed pilot studies to demonstrate that Illumina Arrays are superior to Affymetrix Arrays and have developed a gene list with Drs. Perou, Tuck and Harris to create a custom Illumina DASL(TM) array. In addition, they have performed a pilot study using DNA from archived tissue hybridized to Agilent CGH Arrays. They have shown the characteristic ‘saw tooth’ pattern of a triple negative tumor using this platform as published by Hicks et al. This platform will be used for further analysis. Finally, the Rimm Lab has developed proteomic biomarkers of response to paclitaxel and trastuzumab which will be applied to this cohort. The researchers look forward, in the next six months, to profiling the cohort of 300 tumors in an effort to validate and discover new biomarkers which predict response to paclitaxel and trastuzumab.

Bio:
Dr. Lyndsay Harris is a nationally recognized expert in breast cancer treatment and research. She is an Associate Professor of Medicine, Medical Oncology, at the Yale School of Medicine and the Director of the Yale Cancer Center Breast Cancer Program. Additionally, she serves as Co-Director of the Yale-New Haven Breast 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. Previously, Dr. Harris served as an Assistant Professor at the Dana Farber Cancer Institute and an Attending Physician at the Breast Oncology Disease Center at Dana Farber.

Dr. Harris currently serves a leadership role on several prominent national committees, including as the Associate Chair for Breast Cancer, ASCO Tumor Marker Guidelines Subcommittee, a member of the Cooperative Breast Cancer Tissue Resource Panel of the National Cancer Institute, 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.