Clifford Hudis, MD

2011-2012 BCRF Project:
Rates of obesity and overweight continue to increase in the US, making this a significant public health challenge. In terms of cancer, these conditions are associated with increased risks of breast, colon, high grade prostate, and other solid tumors. In the ongoing close collaboration with BCRF grantee Dr. Andrew Dannenberg at Weill Cornell Medical College (WCMC), Dr. Hudis's team has used laboratory models and human specimens to confirm the link between obesity, chronic localized inflammation in the breast, and increased activity of aromatase, the enzyme that generates the female hormone, estradiol. This can explain, in part, the observed epidemiologic association between obesity and increased risk of postmenopausal breast cancer and suggests that not only weight control, but also anti-inflammatory interventions, could be effective prevention and/or treatment for breast and other cancers. In the past, use of aspirin and other available inflammatory inhibitors that target cyclooxygenase (COX) enzymes, has been associated with a reduced risk of hormone receptor positive breast cancer as well as other cancers. To translate this group's work into the clinic, the researchers have described the "inflammatory index," which is a quantification of the severity of crown-like structures of the breast ("CLS-B") that they discovered in their earlier studies of obese women as predicted by laboratory models. They now plan to increase their understanding of this lesion and its effect through 1) increased acquisition of tissues from human breasts, 2) acquisition of non-breast adipose tissues, and 3) the development of a bank of blood and serum that will be suitable for the development of clinically feasible biomarkers of CLS in multiple tissues. This group's long-term goal is to develop such markers and use them to select patients for prevention and treatment studies and to assess the impact of interventions in a non-invasive fashion.

Mid-year Progress: Dr. Hudis's team continues to expand their studies of the link between inflammation and breast cancer. Based on their work to date, this team's overall hypothesis is that obesity-related breast inflammation is a modifiable risk factor for breast cancer in women. Hence, they predict that drugs, or other interventions that reduce obesity-related breast inflammation, will decrease the risk of breast cancer and that this will also be true in women with non-obesity associated breast inflammation. Also, Dr. Hudis's team believes that it will be important to determine whether some of the known molecular changes that occur in the visceral fat of obese women and contribute to insulin resistance also occur in the breast. To achieve their research goals, they will continue to collect breast tissue from women (normal, overweight, obese) who undergo mastectomy at Memorial Sloan-Kettering Cancer Center. For the next six months, the team expects to complete specimen acquisition and proceed with analysis. Additionally, they plan to recruit a total of 20 male breast cancer patients, five of whom have already been enrolled, for up to another two years. Also, the team will continue to build a blood and serum bank suitable for subsequent exploration to develop non-invasive markers of inflammation. These samples will be stored for possible use in the future to identify a serum/plasma marker of the presence of inflammatory foci in breast. In addition, Dr. Hudis's team will collect and analyze samples to help determine whether the histology and biology of abdominal subcutaneous fat mirrors that of the breast. This effort is a first step towards their future goal of developing rational lifestyle and pharmacological interventions to reduce breast inflammation and presumably decrease the risk of breast cancer and potentially improve outcomes in survivors. If the biology of abdominal subcutaneous fat mirrors breast white adipose tissue, this surrogate tissue could be serially sampled in future intervention studies. Through January 31, 2012, the team has activated this protocol and accrued their first five cases. They will analyze these specimens in an ongoing basis.

Bio:
Clifford Hudis, MD, 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, where he is co-Leader of the Breast Disease Management Team. He has recently been elected President of the American Society of Clinical Oncology (ASCO) for the 2013 academic year. He serves also as a member of the Board of Directors (as Treasurer) of ASCO and is co-Chair of the Breast Committee of the Alliance for Clinical Trials in Oncology (formerly the Cancer and Leukemia Group B). In addition, 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 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. In 2007, Dr. Hudis was appointed as Chairman of The Breast Cancer Research Foundation's Scientific Advisory Committee.