Lisa A. Carey, MD

2009-2010 BCRF Project:
Why one woman gets breast cancer while another, seemingly similar, woman does not, remains largely a mystery to breast cancer researchers. Recent studies have clarified that one of the challenges is that breast cancer is comprised of several biologically distinct molecular subtypes. In addition, while we can to an extent predict the responsiveness of breast cancers to targeted therapy such as anti-estrogen or anti-HER2 therapy, we have little ability to understand who benefits best, and is harmed the least, by chemotherapy. New genetic approaches that are capable of comprehensively examining the genetic makeup of the woman and the breast cancer that she developed promise to help us better unravel these mysteries.

LCCC 9830 is a BCRF-supported clinical trial in which Dr. Carey and colleagues will collect genetic material from 1,000 breast cancer patients and 1,000 healthy women of similar age, race, and ethnicity. While LCCC 9830 is a very large study, it is nearly 80% complete, and the researchers are beginning the sub-studies within this trial that will help them to better understand breast cancer risk and response to treatment. In this pharmacogenomic sub-study project, they will examine the patients in LCCC 9830 who were treated with chemotherapy before surgery to remove their tumor, a unique group of patients in whom they can directly measure responsiveness of their breast cancer to the chemotherapy that is given.

The genetic material collected at enrollment to the study will be used to identify which women have known mutations in several important genes. Each of these mutations have been shown to impact the production or function of a protein that plays a role in the activation, distribution, and/or elimination of one or all of the chemotherapeutic agents administered to these patients. By comparing the gene mutations in responders with those in non-responders, the researchers can validate which mutations are associated with differences in treatment outcomes. They will also examine the whole genetic makeup of the woman and the molecular subtype of her breast cancer, which will help them understand the causes of different kinds of breast cancer.

Mid-Year Progress Report:
Breast cancer behavior is controlled by many factors. The term "breast cancer" is actually inaccurate since researchers now know that breast cancer is a family of biologically distinct diseases. We now realize that the different subtypes of breast cancer have clinical implications, not only for targeted therapy, but also for response to chemotherapy. However, this focus on the breast cancer itself ignores the crucial contribution of the normal tissues of the body to treatment effect. This contribution comes from the tumor microenvironment, which can affect the tumor directly or indirectly through variations in local factors and blood vessels, or it comes from the body’s handling of the drugs that we administer. The focus of this grant is on the latter effect.

Researchers know that when the same dose of drug is given to different women, the amount of that drug that circulates and the time it takes to be metabolized can vary enormously from woman to woman. In addition, certain drugs need to be activated by enzymes in the body to be effective. Dr. Carey and her team hypothesize that variations in the genes that control chemotherapy drug metabolism actually play a significant role in response to therapy. To test this, they are examining the DNA from normal blood obtained from women who are undergoing chemotherapy for their breast cancer. They will look at several genes that have been implicated in the metabolism of specific drugs and compare the genetic variability to the measured response to chemotherapy.

This study has collected germline DNA, exposure and risk factor history, tumor samples, and clinical, treatment and outcome data to date in approximately 850 of a planned 1000 women with newly diagnosed breast cancer, and the researchers are actively collecting similar data from age- and race/ethnicity-matched women without breast cancer. Progress to date includes DNA processing from all participating study subjects, and genotyping in a cohort selected for evaluation of drug metabolizing gene variability and response to therapy

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.