Carol J. Fabian, MD
Professor of Internal Medicine
Kansas Masonic Cancer Research Chair
Director, Breast Cancer Prevention and Survivorship Centers
University of Kansas Medical Center
Kansas City, Kansas
2013-2014 BCRF Project:
(The ANN INC. Award)
Dr. Fabian’s over-arching purpose is to develop prevention strategies which will favorably impact overall health without reducing quality of life. Excess breast cancer risk associated with obesity is thought to be mediated by chronic inflammation resulting in an excess of inflammatory cell (macrophage) infiltration into breast and other fat. This in turn results in an imbalance of fat hormones called adipokines, inflammatory mediators called cytokines, increases in insulin, estradiol and testosterone, and increases in ductal cell proliferation and abnormal cell survival, all risk biomarkers for breast cancer. Dr. Fabian’s team has found in a pilot partially supported by BCRF that improvement in these breast cancer risk biomarkers is significant only with a 10% or greater weight loss which is achieved by ~50% or less of women undergoing a structured weight loss intervention. The marine omega-3 fatty acids EPA and DHA’s ability to resolve chronic inflammation makes them ideal partners with weight loss both for general health as well as breast cancer risk reduction especially for obese individuals unable to achieve or sustain a weight 10% loss. The mechanism by which EPA and DHA reduce inflammation is not completely clear but likely due in part to a decrease in macrophage infiltration into breast fat and production of inflammatory mediators called cytokines. With BCRF funds, Dr. Fabian’s team has just completed two omega-3 pilots May 2013 in 35 pre and 34 postmenopausal average weight women. After six months of 3.4 grams/day of DHA+EPA (Lovaza®) women showed reduction in the breast cancer risk biomarkers proliferation and cellular atypical appearance. In addition, in postmenopausal women there was reduction in breast MCP-1 a molecule responsible for macrophage infiltration, and an improvement in blood levels of the adipo-cytokines adiponectin, and TNF alpha both thought to be risk biomarkers for breast cancer. These results have been presented at 2013 American Association for Cancer Research (AACR) and American Society of Clinical Oncology (ASCO) meetings and have been submitted to 2013 San Antonio Breast Cancer Symposium. Assessment of some of the more specialized biomarkers will be ongoing through the remainder of 2013.
Dr. Fabian’s translational partner, fellow BCRF grantee Dr. Stephen Hursting (University of Texas at Austin), demonstrated in 2013 that EPA + DHA at similar blood levels as the human studies was associated with a marked increase in the anti-inflammatory/pro-resolving derivatives and marked decrease in pro-inflammatory prostaglandins and cancer volume in an obese laboratory model with estrogen receptor-negative (ER-) breast cancer. Researchers at the University of Kansas will complete an ongoing study this year of intermittent vs continuous calorie restriction +/- EPA + DHA in an obese laboratory model that develops ER+ breast cancer. Dr. Fabian proposes to study whether marine omega-3 fatty acids (EPA + DHA) augment the effects of a six month weight loss attempt on breast cancer risk biomarkers in 70 obese post and peri-mebnopausal women compared to weight loss + placebo.
Dr. Fabian’s goal is to conduct a 6 month Phase II biomarker-based pilot trial of a proven weight loss intervention plus a randomization to placebo or omega-3 fatty acids (eicosapentaenoic acid, EPA, and docosahexaenoic acid, DHA) in post-menopausal women at increased risk for development of breast cancer. The clinical trial protocol has been written and is now undergoing institutional review. The researchers are I n the process of finalizing arrangements company that will supply the omega-3 fatty acids and matched placebo. It is anticipated that the trial will be open to accrual in March. In the meantime, the researchers are actively screening potential subjects by both random periareolar fine needle aspiration and blood tests to identify subjects that meet the required eligibility criteria. This will allow the first group to begin intervention as soon as the final approval is obtained, and provide for a rapid accrual.
Carol Fabian received her MD, internal medicine and oncology training from the University of Kansas School of Medicine in Kansas City, Kansas. Dr. Fabian joined the faculty at the University of Kansas Medical Center in 1977 and currently holds the rank of Professor. She serves as the Director of the Breast Cancer Prevention and Survivorship Centers. These Centers are heavily involved in translational research in addition to providing clinical services. She leads the Cancer Prevention Research Program within the University of Kansas Cancer Center and holds the Kansas Masonic Cancer Research Chair.
Dr. Fabian pioneered the use of random periareolar fine needle aspiration to acquire breast epithelial cells for refinement of breast cancer risk assessment and for evaluation of biomarkers as a means of monitoring response in early phase breast cancer prevention clinical trials. Subsequently she has trained investigators at multiple institutions in the use of this technique for research purposes. She is currently the principal investigator of three National Cancer Institute funded grants assessing the effects on breast cancer risk biomarkers of potential prevention strategies: 1) weight loss; 2) a flaxseed derivative; and 3) an aromatase inhibitor in postmenopausal women taking hormone replacement. The translational nature of her work and long-term relationships with her basic science colleagues in cancer biology (Bruce F. Kimler, PhD) and reproductive endocrinology veterinary medicine (Brian K. Petroff, DVM, PhD) have facilitated the development of this BRCF project.