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BCRF Grantee Since


Donor Recognition

The Bloomingdale's Award

Area(s) of Focus

Michael F. Press, MD, PhD

Harold E. Lee Chair in Cancer Research
Norris Comprehensive Cancer Center
University of Southern California
Los Angeles, California

Current Research

Estrogen receptor (ER) protein in breast cancer cell nuclei has been a useful therapeutic target for treatment of breast cancer patients since the 1980s. Estrogen receptor in tumor cell nuclei facilitates responsiveness to circulating estrogen hormones in both normal tissues and in breast cancer cells. Approximately 70% of breast cancers have ER protein expressed, and these cancers respond to estrogens with stimulation of tumor cell division. An established treatment for ER-positive breast cancers is treatment with hormone-like inhibitors of ER action to inhibit tumor cell growth or reduction of estrogen levels in post-menopausal women through inhibition with aromatase inhibitors. Because ER is such an important growth regulator of breast cancer cells there has been a largely unproductive search for mutations in the gene that encodes ER, known as ESR1.

Gene amplification is a type of genetic alteration in which a region of a chromosome containing one or more genes is duplicated, usually in tandem, many times over so the genes in this region of the chromosome are represented not by a single copy of the gene on that chromosome but by many copies of the gene. This duplication or amplification of a gene would facilitate the production of large quantities of the protein encoded by this gene. Although Dr. Press's team did not find amplification of ESR1, they have preliminarily shown that other genes, known as ER coactivators, are amplified in some breast cancers. This observation has important implications for women who have breast cancer. It suggests that ER coactivators may be present at high levels in some cancers facilitating responses by ER to lower levels of estrogen stimulation. In their preliminary investigations they have also found mutations in the genetic sequence of some of the coactivators of ER. These observations suggest a potential effect on responsiveness to anti-estrogen therapy. The goals of Dr. Press's investigations are 1) to confirm that ER coactivator genes are indeed altered, either amplified or mutated, in human breast cancers, 2) to determine if these ER alterations in cancers are more (or less) responsive to anti-estrogen therapy, and 3) to use human breast cancer cell lines to model response to endocrine therapy in cancers with and without ER coactivator gene amplification. If breast cancers with ER coactivator gene alterations were particularly responsive (or unresponsive) to hormonal treatments, this could substantially alter the need for these women to be treated with chemotherapy.

Mid-Year Summary

Preliminary results from Dr. Press’s group and others suggest that changes in additional ER regulators may play important roles in responsiveness to anti-estrogen therapies. Their study will determine if HER2 co-amplified genes are associated with resistance to anti-estrogen treatments. The researchers have identified 11 regions in the human genome that are significantly co-altered (co-amplified) with HER2 in breast cancer. The region most frequently co-altered with HER2 is located on the same chromosome with HER2 and contains as many as 60 other genes. They have identified a gene, known as MYST2, that is not only co-amplified with HER2 in approximately 40% of HER2-amplified human breast cancer cell lines and human breast cancers but also has functions which suggest it might modify responses to anti-estrogen therapy. They have used human breast cancer cell lines in culture to demonstrate that MYST2 co-amplification does indeed reduce breast cancer cell response to tamoxifen anti-estrogen therapy. They have developed assays that permit evaluation of the status of MYST2 in stored breast cancer tissues from women who participated in large clinical trials to determine if co-amplification of MYST2 is associated with lack of response to anti-estrogen therapy. This work is currently in progress.


Dr. Michael F. Press is a board certified pathologist who has authored or co-authored more than 180 papers and is recognized for his work in characterizing molecular genetic alterations of breast cancer. He is a Surgical Pathologist at the USC+Los Angeles County Hospital and the USC Norris Comprehensive Cancer Center where he is a Professor of Pathology and holds the Harold E. Lee Chair in Cancer Research. He was formerly an Assistant Professor and Associate Professor of Pathology and a Surgical Pathologist at the University of Chicago (1981-1987), where he received both his medical and doctoral degrees.

Dr. Press is the director of a reference laboratory (USC Breast Cancer Analysis Laboratory) engaged in private practice pathology on a referral basis (1988-present). In this laboratory he evaluates prognostic markers and predictive markers as well as histopathology used in making treatment decisions for women with breast cancer. He is the director of the central laboratory for the Cancer International Research Group (CIRG), a clinical trials organization that evaluates new therapies in predominantly breast cancer patients but also conducts trials in several other cancers including gastric cancer.

His particular 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. The most prominent area of activity for his laboratory has been in the study of the human epidermal growth factor receptor type 2 (HER-2) 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 HER-2 as a target for therapy.

Dr. Press is active in teaching medical students, graduate students, postdoctoral fellows and resident physicians.