University of Kansas Medical Center
Kansas City, Kansas
Professor of Internal Medicine
Director, Breast Cancer Prevention and Survivorship Centers
Morris Family Endowed Chair in Cancer Prevention
To develop strategies to prevent breast cancer in moderate- to high-risk women and to improve health and quality of life for breast cancer survivors.
Chemoprevention drugs such as tamoxifen or aromatase inhibitors, dramatically reduce the risk of developing breast cancer, but many women will discontinue their use due to side effects that can initiate or worsen menopausal symptoms. Hormone replacement therapy (HRT) is the most effective way to reduce the vasomotor symptoms of menopause (hot flashes, flushing and night sweats), but there is concern that HRT might increase the risk of developing breast cancer, particularly in women with a higher-than-average risk. Dr. Fabian is focused on finding effective alternatives to tamoxifen and aromatase inhibitors that do not cause unwanted side effects. In prior studies, her team showed that women that took a combination of bazedoxifene and conjugated estrogen (BZA-CE) had a reduction in breast density and breast tissue proliferation (cell growth) as well as a reduction in blood progesterone, testosterone, and IGF-1 levels—factors known to promote breast cancer growth. Her team is building on these observations and testing a BZA-CE combination as safe alternatives to current hormone-based chemoprevention in women at risk of breast cancer.
Dr. Fabian and her colleagues are conducting a multi-institution Phase II NCI-sponsored randomized clinical trial of the BZA-CE combination versus placebo to assess its effects on risk-associated biomarkers. They are also testing alcobifene, the conjugated estrogen component of BZA-CE, as a potential chemo-preventive agent that will not result in side effects as seen with tamoxifen and aromatase inhibitors. Prior to the trial launch, they identified candidate biomarkers, such as genes and their corresponding proteins that are affected by estrogen, that could be used to assess efficacy of the treatments. Automated measures of breast density and MRI as secondary biomarkers were also examined. Preliminary lab results indicate that, unlike tamoxifen, neither the combination nor alcobifene alone, increased the expression of the candidate biomarkers.
She and her team will continue to accrue patients into the clinical trial with BZA-CE to determine its potential use in chemo-preventive strategies. Based on their preclinical findings, they will launch a clinical trial with alcobifene alone. Results of these studies may identify more acceptable prevention strategies with fewer side effects for women at increased risk for breast cancer, as well as biomarkers to better predict which women will most likely benefit from the treatment.
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 Morris Family Endowed Chair in Cancer Prevention.
Dr. Fabian pioneered the use of random peri areolar fine needle aspiration to acquire breast epithelial cells for refinement of breast cancer risk assessment. The technique is also used for evaluation of biomarkers to monitor response in early phase breast cancer prevention clinical trials: 1) weight loss in combination with omega-3 fatty acid supplementation; 2) a flaxseed lignin derivative; and 3) an aromatase inhibitor in postmenopausal women taking hormone replacement. She is also involved in clinical studies to promote health and quality of life for breast cancer survivors and serves as a Co-Chair for the Cancer Survivorship Committee of SWOG.
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