Lisa A. Carey, MD

On Behalf of Cancer and Leukemia Group B
Made possible by generous support from Macy's
Co-Invesigators: Richard L. Schilsky, MD, Chairman, Cancer and Leukemia Group B, Chicago; Matthew J. Ellis, MD, PhD, Washington University School of Medicine, St. Louis, MO; and William M. Sikov, MD, Brown University, Providence, RI

Over the past several years, with support from BCRF, Cancer and Leukemia Group B investigators have undertaken a series of large-scale clinical trials that are leading to important improvements in breast cancer therapies: One project is utilizing new technology to generate genetic profiles of breast cancer tumors and to identify which genetic markers are associated with response to paclitaxel chemotherapy. The identification of these markers may make it possible to predict which patients are most likely to respond to paclitaxel treatment. Another project is studying the unique biological characteristics of breast cancer that occurs in older women. This work is a companion to a recently completed clinical trial studying adjuvant chemotherapy in older women with breast cancer. Another project is evaluating magnetic resonance imaging (MRI) and spectroscopy (MRS) and various molecular markers as predictors of clinical response in women receiving chemotherapy and radiation for locally advanced breast cancer.

In another CALGB project, genetic analysis of breast tumors is being used to determine which patients are most likely to benefit from use of paclitaxel as part of adjuvant chemotherapy. In another, biomarker and genetic analyses of breast tumors are being used to determine which patients are most likely to benefit from use of dose dense chemotherapy. And another will correlate tumor epidermal growth factor receptor and Her2 expression with the clinical outcomes of women receiving fulvestrant with or without lapatinib, a novel drug that inhibits EGFR and Her2. The goal of the project is to develop markers to guide patient selection for future therapies targeting the epidermal growth factor receptor.

And two additional CALGB clinical trials, expected to activate in Fall 2007, deal with advances in the postoperative treatment of breast cancer which have led to new challenges in drug development. Recurrence rates from breast cancer have declined substantially in recent years. While there is no question that the decline in recurrence is good news, it has led to an increasing need to conduct very large clinical trials in order to detect small benefits. In addition, it often takes years before results are available. The preoperative administration of systemic therapy (e.g. chemotherapy, hormonal therapy, targeted therapy) is safe and effective. In addition, from a research standpoint, it has two major benefits: 1) we can quickly see whether drugs shrink the cancer and 2) we can study the cancer cell before and after treatment to assess the impact of our therapies.

CALGB researchers are going to test two new targeted therapies using this approach. In patients with tumors that are dependent on HER2, they will compare trastuzumab (Herceptin) versus lapatinib (Tykerb) versus both. In patients with hormone receptor-poor/HER2-negative tumors (often referred to as triple negative or basal-like), they will test the addition of an antibody that shuts off new blood vessel formation (Avastin or bevacizumab).

These studies represent a unique opportunity for the CALGB as its researchers will have the ability to see the effects of these treatments on tumors before surgery and they will be able to gather extensive tissues for later study. With support from BCRF, they will build and maintain the infrastructure needed to collect these tissues, store them until the clinical study is completed, distribute them to collaborating investigators, and perform studies on them. The results of this program will include an increased understanding of how available therapeutics kill cancer and improve treatment approaches. BCRF funds in the coming year will be used for the collection and storage of breast cancer biopsies obtained from patients enrolled in both studies.

Mid-Year Progress Report:
Dr. Schilsky reports that for the project utilizing new technology to generate genetic profiles of breast cancer tumors and to identify which genetic markers are associated with response to paclitaxel chemotherapy, CALGB anticipates that the gene expression data to be available in the next 3 months and primary data analysis to be completed within 6 months. For the project studying the unique biological characteristics of breast cancer that occurs in older women, the researchers report that a total of 633 patients enrolled in the clinical trial and 588 patients registered to the correlative science component. All tissue analysis for IHC has been completed, and CALGB researchers are in the process of data transfer and cleaning up in preparation for analysis. They expect to submit an abstract to the 2008 ASCO Breast Cancer Symposium.

For the BCRF-supported Correlative Studies in Neoadjuvant Trials for Locally Advanced Breast Cancer, magnetic resonance imaging (MRI) and spectroscopy (MRS) and various molecular markers are being evaluated as predictors of clinical response in women receiving chemotherapy and radiation. In another BCRF-funded project, genetic analysis of breast tumors is being used to determine which patients are most likely to benefit from use of paclitaxel as part of adjuvant chemotherapy. In another, biomarker and genetic analyses of breast tumors are being used to determine which patients are most likely to benefit from use of dose dense chemotherapy. Another CALBG project aims to correlate tumor epidermal growth factor receptor and Her2 expression with the clinical outcomes of women receiving fulvestrant with or without lapatinib, a novel drug that inhibits EGFR and Her2; the study was activated in September 2006. In the two trials (1) comparing Herceptin versus Tykerb, and 2) testing Avastin, the trial concepts have been approved by NCI and protocols are being finalized with activation anticipated in early 2008.

Bio:
Lisa Carey is an Associate Professor in the UNC Department of Medicine, Division of Hematology-Oncology. She graduated from Wellesley College in 1984 with a BA in Biology and Art History, before receiving a MS in Physiology from the University of Kentucky. She received an MD from the Johns Hopkins University School of Medicine in 1990. After a residency in Internal Medicine also at Johns Hopkins, she stayed at Johns Hopkins for a fellowship in Medical Oncology. During her fellowship she completed a ScM. in Clinical Research. Dr. Carey joined the UNC faculty in 1998. She has served since 2003 as the Medical Director of the UNC Breast Center and is the UNC-Lineberger Comprehensive Cancer Center (UNC-LCCC) Protocol Office Executive Committee Breast Disease Group Leader as well as the UNC-LCCC Protocol Review Committee Breast Cancer Chair.

Dr. Carey has a well-defined interest in clinical/translational research in breast cancer, with a particular interest in the clinical implications of different molecular subtypes of breast cancer. She both designs and leads clinical trials as well as working often and well with laboratory investigators. She has successfully translated bench efforts from laboratory science collaborators into clinical research. She was the lead author of a recently published article in JAMA examining racial disparities among breast cancer subtypes. She is the principal investigator (P.I.) of several clinical trials, including a multicenter inter-SPORE (Specialized Program of Research Excellence, National Cancer Institute [NCI]) Phase II study of targeted therapy in metastatic basal-like breast cancer (a subtype identified by gene expression array). This heavily funded trial includes both clinical and laboratory participation from UCSF, Dana Farber, Duke University, Georgetown, Johns Hopkins, Baylor, Washington University, University of Alabama-Birmingham, Mayo, and M.D. Anderson Cancer Center, and is a testament to her ability to provide clinical leadership in translational and early clinical research.

Dr. Carey is the P.I. of a recently published multicenter Phase II study incorporating biologic therapy into chemotherapy for locally advanced breast cancer as well as a proposed cooperative group neoadjuvant trial examining several HER2-targeted strategies for Stage II-III HER2-positive breast cancer. She is the clinical liaison for several correlative science collaborations, including both institutional and cooperative group trials that correlate nucleic acid and protein characterization of breast cancers with response to neoadjuvant therapy.

Dr. Carey has served on the American Society of Clinical Oncology (ASCO) Scientific Program Committee and as faculty for the ASCO annual meeting for several years. She was named to the Cancer and Leukemia Group B (CALGB) Breast Core Committee in 2003. She was awarded a Doris Duke Clinician Scientist Award in 1999 and a Career Development Award from the NCI in 2000.