Lisa A. Carey, MD
Physician-in-Chief, North Carolina Cancer Hospital
Chief, Division of Hematology-Oncology, UNC School of Medicine
Preyer Distinguished Professor in Breast Cancer Research
Medical Director, UNC Breast Center
Lineberger Cancer Center
University of North Carolina
Chapel Hill, North Carolina
2013-2014 BCRF Project:
(The Pink Promises Award)
Breast cancer is a heterogeneous disease, made up of several biologically distinct subtypes. Within these subtypes are variations in growth, survival, and behavior that are poorly understood. HER2-positive (HER2+) breast cancer, once one of the most aggressive subsets, has been transformed by the development of HER2-targeting drugs such as trastuzumab (Herceptin®), lapatinib (Tykerb®), and pertuzumab (Perjeta®). Recent studies suggest that doctors may do even better with adding these drugs together rather than giving them alone. A large clinical trial, CALGB 40601, designed to examine single HER2-targeting with trastuzumab added to neoadjuvant (preoperative) chemotherapy compared with the same drugs with the addition of a second HER2-targeted drug, lapatinib. This trial, supported by the National Cancer Institute and reported in June 2013, found a modest increase of 10% in the proportion of women with eradication of the tumor in the breast with both drugs compared with just one.
With BCRF support, Dr. Carey’s team obtained research biopsies from all women participating in CALGB 40601, and examined the molecular subtypes contained within HER2-positive disease. They found that even within this clinically defined subset, there was marked molecular heterogeneity. About 1/3 of the tumors were biologically defined by HER2 signaling, called the “HER2-Enriched” subtype, which had the highest responsiveness, but a significant number were actually luminal tumors, which are more biologically driven by hormone receptors and had lower responsiveness. The remainder included subtypes such as the basal-like subtype that is typically associated with triple negative disease. This heterogeneity, which has been the emerging story of breast cancer for the past few years, may have substantial implications for who needs more aggressive HER2-targeting treatments and who can be treated just as successfully with less aggressive regimens.
This project is identifying the impact of increasingly recognized breast cancer biologic heterogeneity and intrinsic subtypes on breast cancer behavior and response to therapy. Triple negative breast cancer (TNBC) is an aggressive clinical subset of breast cancer, in which chemotherapy is currently the sole option to reduce recurrence or treat metastatic disease. Previous BCRF funds have supported CALGB 40601, a randomized phase III study of neoadjuvant paclitaxel with trastuzumab, lapatinib, or both. BCRF data provided important insight into the molecular determinants of response in this trial and set up the mechanism by which we can do similar work in TNBC trials. CALGB 40603 is a randomized phase II study supported by the National Cancer Institute that was designed to answer two questions relevant in TNBC: first, whether a chemotherapy drug called a platinum drug, and second, whether bevacizumab, a drug that combats the cancer’s ability to feed itself, are especially useful in TNBC. CALGB 40603 found that the addition of carboplatin to standard neoadjuvant chemotherapy significantly increased the pathologic complete response in the breast and in the breast plus axillae and that Bevacizumab also has some effect when added to chemotherapy, but due to its toxicity was felt to be a less promising approach (SABCS, Dec 2013, Abstract S5-01).
With BCRF support, Dr. Carey’s team obtained research biopsies from the approximately 400 women participating in CALGB 40603, and will examine the molecular subtypes contained within TNBC since the molecular heterogeneity that has become clear over the past few years, may have substantial implications for who might benefit from more aggressive chemotherapy regimens, from platinum drugs, and from antiangiogenic approaches. As of January 10, 2014, RNA extraction and DNA extraction has been completed on all 482 samples from 40601 and all 647 samples from 40603. All 40603 samples passing RNA QA have undergone RNA-seq. There are 150 samples from 40601 that will undergo RNA-seq and be completed soon. Once completed, the researchers will apply the remaining BCRF funds towards resuming work on performing comprehensive gene expression profiling for several validated signatures, including intrinsic subtype (Luminal A, Luminal B, HER2-Enriched, Basal-like, Claudin-Low) and four other signatures (including hypoxia and proliferation signatures) on patients who have been enrolled in the population-based study, LCCC 9830.
Lisa A. Carey, MD is the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research in the UNC Department of Medicine, Division of Hematology-Oncology. She graduated from Wellesley College in 1984 with a bachelor's degree in Biology and Art History. She received her medical degree from the Johns Hopkins University School of Medicine in 1990. She remained at Johns Hopkins for her residency in Internal Medicine followed by a fellowship in Medical Oncology and an advanced degree in Clinical Investigations. Dr. Carey joined the UNC faculty and Lineberger Comprehensive Cancer Center in 1998. In 2012, she was appointed Chief of the Division of Hematology-Oncology and Physician-in-Chief of North Carolina Cancer Hospital. Dr. Carey is Medical Director of the UNC Breast Center.
Dr. Carey has a longstanding research interest in the clinical application of laboratory findings in breast cancer, with a particular interest in the
clinical implications of different molecular subtypes of breast cancer. She designs and leads clinical trials of novel drugs and approaches, and is a close
collaborator with several laboratory investigators and epidemiologists. Dr. Carey has served on the American Society of Clinical Oncology (ASCO) Scientific
Program and Education Committees and as faculty for ASCO and AACR-CTRC San Antonio annual meetings for many years. She was awarded a Doris Duke Clinician
Scientist Award in 1999, a Career Development Award from the National Cancer Institute (NCI) in 2000, and was inducted into the Johns Hopkins Society of
Scholars in 2008. In 2011 Dr. Carey was awarded the National Cancer Institute Director's Service Award.