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BCRF Grantee Since

2004

Donor Recognition

The Cynthia Lufkin Award

Clifford Hudis, MD

Chief, Breast Cancer Medicine Service and Attending Physician
Memorial Sloan Kettering Cancer Center
Professor of Medicine, Weill Cornell Medical College
New York, New York
Immediate Past President, American Society of Clinical Oncology (ASCO)
Chairman, BCRF Scientific Advisory Board

Current Research

Obesity and being overweight are increasingly recognized as promoting the development and progression of malignancy, including hormone-sensitive breast cancer. Obesity is expected to replace tobacco as the most common modifiable risk factor for several common cancers. The specific malignances associated with obesity/overweight include breast, colon, high-grade prostate, and other solid tumors. In the past year, Dr. Hudis’s team has continued to make significant progress in their understanding of the mechanism by which obesity/overweight influences the development and growth of cancer. Through their longstanding close collaboration with BCRF grantee, Dr. Andrew Dannenberg at Weill Cornell Medical College, Dr. Hudis’s group has confirmed that their laboratory models of obesity are accurate predictors of the observations they are making in specimens from patients. Therefore, based on biomarker results from the laboratory, they are now extending their work in patients to 1) develop noninvasive methods of detecting obesity-related inflammation, 2) to determine clinical factors that alter obesity-related inflammation, and 3) to pursue potential lifestyle and therapeutic interventions for use in targeted subsets of overweight and obese women. Increasingly, they see evidence that their work is relevant to other malignancies as well.

In the coming year, the research team’s primary objective will be to better understand the clinical implications of obesity related inflammation and ways to better detect and protect against the associated increase in cancer risk and progression. To do this, they will continue collecting human tissues in order to build a biobank that is sufficient to allow answers to clinical questions by correlating their prospectively maintained clinical database with analyses of the human specimens in the lab of their collaborator, Dr. Andrew Dannenberg. Specifically, Dr. Hudis’s team will determine if specific patient characteristics, such as age and menopausal status, are associated with more severe inflammation and if any of those characteristics, such as the use of statins or metformin, are protective. Additionally, they will continue to collect paired tissue and blood samples to determine if a blood-based signature of biomarkers is an accurate way to predict inflammation. Finally, based on ongoing preclinical studies in the Dannenberg laboratory, they plan to initiate a human pilot study in which will they determine whether celecoxib will suppress levels of PGE2 and aromatase in obese women. These studies could position the researchers to launch large scale prospective intervention trials in the future.

Mid-Year Summary

Obesity is a risk factor for the development of several common malignancies including hormone receptor positive disease breast cancer in postmenopausal women.In collaboration with grantee Andrew Dannnenberg, Dr. Hudis’s team made the pivotal observation that most overweight and obese women have a low grade inflammation of the white adipose of the breast, identified by the presence of “crown-like structures” (CLS-B). This lesion consists of a dead or dying adipocyte (fat cell) surrounded by activated macrophages (scavenger cells). A key aspect of this inflammatory lesion is that it generates a series of molecules that ultimately increase aromatase activity resulting in more production of estrogen. This then provides a plausible explanation for the seeming clinical paradox of increased risk for hormone (estrogen)-driven breast cancer after ovarian estrogen production has fallen in post-menopausal women. Simply stated, low-grade chronic inflammation of the fatty tissues of the breast may provide the necessary estrogen to promote breast cancer growth. The researchers’ overall goal is to identify individual women at risk for breast cancer or for a poor prognosis after its diagnosis because of inflammation and develop effective interventions including diet and/or drugs. This year’s project extends and complements the laboratory work of Dr. Hudis’s collaborator (Dannenberg) by obtaining additional clinical samples, developing a potential blood test for this specific inflammatory process, and establishing the generalizability of their observations at other sites of fat deposition.

Bio

Clifford Hudis, MD, Chairman of BCRF Scientific Advisory Board, is Chief of the Breast Cancer Medicine Service and Attending Physician at Memorial Sloan Kettering Cancer Center (MSKCC) in New York City. He is also a Professor of Medicine at the Weill Cornell Medical College and the Immediate Past President of the American Society of Clinical Oncology (ASCO).

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, where he is co-Leader of the Breast Disease Management Team. He is also co-Chair of the Breast Committee of the Alliance for Clinical Trials in Oncology (formerly Cancer and Leukemia Group B). In addition, Dr. Hudis is a member of the Steering Committees of the Translational Breast Cancer Research Consortium (TBCRC) and the North American Breast Cancer Group (NABCG), and a member of National Cancer Institute’s Breast Cancer Correlative Science Committee.

Dr. Hudis’s research includes the development of a wide range of novel drugs and the study of relevant correlative science endpoints in breast cancer. With his collaborators both at MSKCC and beyond, he has focused his BCRF-supported research on understanding the mechanisms that link diet, obesity, inflammation, and breast cancer risk and outcomes. Building on their discoveries of low grade inflammation in association with overweight and obesity they are now studying interventions that may reduce the risk of breast cancer and of its return. In 2007, Dr. Hudis was appointed as Chairman of BCRF’s Scientific Advisory Committee and in 2012 became Chairman of its Scientific Advisory Board.

Read more about Dr. Hudis in an interview in The Jerusalem Post

Dr. Hudis was recently interviewed about the upcoming Annual Meeting of the American Society of Clinical Oncology (ASCO) and taking office as ASCO President in June 2013. Read more...