Clifford Hudis, MD

2009-2010 BCRF Project:
Co-Investigator: Andrew Dannenberg, MD, Weill Medical College of Cornell University, NY

Drs. Hudis and Dannenberg are exploring the relationship between the COX enzymes (Cox-1 is present in normal tissue whereas COX-2 is increased in response to injury and abnormal growth) and cancer. They have shown that the prostaglandin products of COX enzymes increase formation of proteins including aromatase (the enzyme that makes estrogen). This female hormone can drive breast cancer formation and growth. Because widely available anti-inflammatory drugs inhibit COX enzymes and therefore may lower estrogen level, this work can explain the potential reduction in breast cancer among regular aspirin uses and expand on the use of this kind of cancer prevention approach.

COX enzymes generate prostaglandin products through a series of steps that can be blocked with medications. The researchers' ongoing work is aimed at better identifying the targetable components of this system for which there are (or could be) specific drugs that may both prevent and treat breast cancer. In the past year, they have further described the impact of prostaglandin signaling on the BRCA1 gene and, in turn, its impact on aromatase activity and therefore estrogen production. This increased understanding of the roles prostaglandins and BRCA1 should help to identify better and safer methods of treating and preventing breast cancer.

Since their last report, the researchers have further described the impact of prostaglandin signaling on the activity of the breast cancer gene (BRCA1) and, in turn, its impact on aromatase activity and therefore estrogen production. Moreover, they have new evidence connecting COX-1, the target of aspirin, BRCA1 and aromatase. This increased understanding of the roles of prostaglandins and BRCA1 should help to identify better and safer methods of treating and preventing breast cancer. The primary objective of the new grant year is to further elucidate the role of COX-derived prostaglandins in breast cancer with the overall goal of developing improved preventive strategies.

Mid-Year Progress Report:
In the past year, the researchers have developed a new understanding of how anti-inflammatory agents may reduce the risk of breast cancer. Previously, it was known that COX-1 was present in normal tissue whereas COX-2 levels increase in cancer. The prostaglandin products of COX enzymes stimulate the formation of aromatase, the enzyme that makes estrogen (this female hormone can drive breast cancer formation and growth). Because widely available anti-inflammatory drugs inhibit COX enzymes and therefore may lower estrogen levels, this work helps to explain the observation that the risk of estrogen receptor-positive breast cancer may be reduced among regular aspirin users. Aspirin may have some beneficial effects that are not observed with other anti-inflammatory agents.

Since the last report, Drs. Hudis and Dannenberg have identified new prostaglandin-independent effects of aspirin that may help to explain its ability to reduce the risk of breast cancer. Their increased understanding of how traditional NSAIDs, selective COX-2 inhibitors and aspirin impact on the expression of genes implicated in breast carcinogenesis including BRCA1 and aromatase should help to identify better and safer methods of preventing and treating this disease.

Bio:
Dr. Hudis is Chief of the Breast Cancer Medicine Service and Attending Physician at Memorial Sloan-Kettering Cancer Center in New York City. He is also a Professor of Medicine at the Weill Medical College of Cornell University. A 1983 graduate of the Medical College of Pennsylvania (a combined 6 year BA/MD program with Lehigh University), Dr. Hudis joined the MSKCC faculty in 1991. He is co-leader of the Breast Disease Management Team at MSKCC, co-Chair of the Breast Committee of the Cancer and Leukemia Group B (CALGB), and a member of the Board of Directors (as Treasurer) of ASCO. In 2007 Dr. Hudis was appointed as chairman of The Breast Cancer Research Foundation’s Scientific Advisory Committee. He is a member of the Steering Committees of the Translational Breast Cancer Research Consortium and the North American Breast Cancer Group, and a member of the NCI-Breast Cancer Correlative Science Committee.

His research includes the development of a wide range of novel drugs and study of relevant correlative science endpoints in breast cancer. With his collaborators both at MSKCC and beyond he has recently focused on the development of better molecular tests for genetic abnormalities and variations in cancer, new classes of drugs for several specific subtypes of breast cancer, and the potential role of anti-inflammatory agents as both treatment and prevention. This work has led to a greater appreciation of the subtle genetic variability frequently seen in cancer, the clinical development of several new classes of targeted agents in breast cancer, and a growing understanding of the complex role of inflammation in causing and promoting malignancy.