University of North Carolina
Chapel Hill, North Carolina
L. Richardson and Marilyn Jacob Preyer Distinguished Professor in Breast Cancer Research
Deputy Director of Clinical Sciences, Lineberger Comprehensive Cancer Center
Investigating the biological underpinnings of metastatic breast cancer by conducting in-depth molecular analyses of tumor samples.
Most of what researchers know about breast cancer biology is based on studying the primary cancer, or the cancer at the location where it originates and begins to grow. Less is known, however, about the biology of metastatic breast cancer (MBC), or cancer that spreads from the breast to other organs, and no cure is currently available. Determining the biology at different metastasis sites and how different organs affect cancer behavior informs how researchers make decisions on individualized therapy and treatment.
Dr. Carey and her team are comparing samples from the original breast tumors with metastases in the same patient, subjecting them to cellular and genetic analyses to reveal their differences. They have found that a subset of metastatic tumors did not match the primary tumor characteristics. They did not have the same molecular profile or were a different subtype, such as switching from a luminal primary breast cancer to a more aggressive basal cancer at the metastatic site. Additionally, they found that metastatic breast cancer can evade immune cells, and this behavior also tends to vary by metastatic site.
In the past year, the team has continued their clinical trials to further understand the genomics of metastases and how organ-specific influences impact MBC. At least ten percent of MBC tumors are molecularly different from the clinical subtype of the primary tumor, which may have therapeutic implications. They have observed organ-specific influences in the microenvironment in metastases sites, with variability in immune gene signatures that are particularly low in the liver and brain. The team is also piloting new tests that can differentiate intrinsic subtypes in primary/metastasis tissue pairs.
The team will continue to enroll patients into their ongoing HARMONY trial, from which they will continue their site-specific molecular studies. They will also continue enrolling patients into their Rapid Autopsy Program, a databank that accepts and stores tumor and tissue donations from MBC patients, to further characterize molecular heterogeneity in primary and metastasis cancer sites. Whenever possible, they will co-enroll patients in HARMONY, and AURORA-US program, part of a larger international initiative to conduct precise, multi-level molecular analyses of MBC.
Lisa A. Carey, MD, ScM, FASCO is the L. Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research and Lineberger Comprehensive Cancer Center Deputy Director of Clinical Sciences in the Department of Medicine at the University of North Carolina, Chapel Hill (UNC). Dr. Carey has a longstanding interest in the clinical implications of tumor molecular subtypes and microenvironmental influences on response to therapy and outcomes in 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 graduated from Wellesley College, received her medical degree from the Johns Hopkins University School of Medicine where she remained for her residency in Internal Medicine, followed by a postdoctoral fellowship in Medical Oncology and an advanced degree in Clinical Investigations. She joined the UNC faculty and Lineberger Comprehensive Cancer Center in 1998 and was the Chief of the Division of Hematology and Oncology and Physician-in-Chief of the North Carolina Cancer Hospital from 2012-2020. In 2023, she was appointed the Vice-Chair of the Breast Cancer Research Foundation Disparities Initiative. She has served in many roles for the American Society of Clinical Oncology (ASCO), the American Association for Cancer Research (AACR) and is a member of the Susan G. Komen Scientific Advisory Board. She is a recipient of the National Cancer Institute Director’s Service Award, a Fellow of the American Society of Clinical Oncology (FASCO) and has served as the co-Chair of the Alliance National Cooperative Group Breast Committee since 2017.
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