Harold E. Lee Chair in Cancer Research
Norris Comprehensive Cancer Center
University of Southern California
Los Angeles, California
Predictive markers, such as estrogen receptor (ER) and HER2, play an important role in selecting the most appropriate (targeted) treatment for women with breast cancer. With BCRF support, Dr. Press and colleagues showed that HER2 gene amplification status is correlated with patient response to anti-HER2 therapies, lapatinib and trastuzumab, and that low levels of ER in HER2-negative breast cancers is associated with responsiveness to lapatinib, an inhibitor of both HER2 and epidermal growth factor receptor (EGFR). These observations suggested cross-communication between membrane receptor pathways (EGFR and HER2) and ER-related pathways. In the coming year, Dr. Press and his team are conducting analyses of the new clinical guidelines for HER2 testing to determine whether or not this new classification provides clinically meaningful information. Using the new HER2 classification scheme as specified by the ASCO-CAP guidelines of 2013/2014 they will: 1) Re-evaluate HER2 gene amplification status of breast cancers from patients who were enrolled in clinical trials to determine the effectiveness of trastuzumab in newly diagnosed disease, 2) Assess the role of MYST2, a gene frequently co-amplified along with HER2, as a potential marker of anti-estrogen treatment resistance, 3) Characterize mutations in a gene known as PI3-kinase (phosphatidylinositol-4,5-bisphosphate 3-kinase) using tumor tissue from patients enrolled in clinical trials of HER2 targeted therapies to determine whether or not these mutations play a role in treatment resistance, and 4) Determine whether mutations in ER co-regulator genes (coactivators and/or corepressors) have a role in anti-estrogen resistance. These studies are expected to have both an immediate and potentially long-term impact on personalized medicine for breast cancer patients.
Dr. Press is a Professor in the Department of Pathology and holds the Harold E. Lee Chair in Cancer Research at the University of Southern California’s Norris Comprehensive Cancer Center. Dr. Press is a board certified pathologist, directs the USC Breast Cancer Analysis Laboratory as well as the Central Laboratory for the Translational Research In Oncology (TRIO)/Cancer International Research Group (CIRG), and is Leader of the USC Clinical Laboratories.
His laboratory evaluates prognostic and predictive markers used in making treatment decisions for women with breast cancer. It has served as the Central Laboratory for either retrospective or prospective analyses of tissue specimens for 18 clinical trials that collectively accrued more than 13,000 patients. Dr. Press’s area of research interest is in molecular alterations of breast and gynecologic cancers, especially those that have the potential to be important in either diagnostic or therapeutic decision-making for patient management. His research has been continuously funded by research grants for more than 25 years. He is the author or co-author of more than 200 peer-reviewed publications. The most prominent area of activity for his laboratory has been in the study of the human epidermal growth factor receptor type 2 (HER2) in breast and other cancers. He published his first paper in this area in 1989 (Science 244: 707-712, 1989) and his laboratory is still actively contributing to this area as well as to the conduct of clinical trials evaluating HER2 as a target for therapy.