Carol J. Fabian, MD :: Profile
Professor of Internal Medicine
Kansas Masonic Cancer Research Chair
Director, Breast Cancer Prevention and Survivorship Centers
University of Kansas Medical Center
Kansas City, KS
Tell us about yourself as a scientist and how you became interested in breast cancer research. Did you ever seriously consider another kind of career than that of the sciences?
My interest in science dates back to my early college days. I was first attracted to psychology, then microbiology, and finally medicine. I never did consider another type of career other than the sciences.
I became interested in breast cancer research during fellowship training in oncology. Although I was interested in a variety of different types of cancer, I was particularly drawn to breast cancer because it seemed like so many young women at the time were being affected with the disease.
What factors have motivated you to continue studying this field?
My interest in risk assessment and prevention research came about 15 years after I started treating cancer patients. When I completed training in the 70's there was tremendous excitement in oncology. We thought almost every woman with early breast cancer could be cured with the right combination of adjuvant treatment - whether chemotherapy, anti-hormone therapy, and radiation, in addition to surgery. We just had to find the right combination. That is still the basic premise of treatment research and we have made tremendous strides in the past 35 years. However, after a decade and a half of oncology practice, it became very painfully obvious to me that many women who had early breast cancer were not going to be cured despite doing everything "right." That is, they got their yearly mammograms, the cancer seemed to have been detected early, and they received aggressive adjuvant therapy; yet, many still relapsed and died. Often, these were younger women with small children. It was heartbreaking to see. In addition, many women who did appear to be cured had lingering side effects which reduced their quality of life. Prevention of breast cancer by blocking or reversing precancerous changes with medication rather than waiting for it to happen seemed to make sense.
The early days (circa 1990) of working in risk assessment and prevention were a little tough. Although the concept of "prevention therapy" was coming into its own, drug therapy has side effects, which for women who are not destined to get the disease could completely avoid. We needed tools to predict who was at highest short-term risk and who was likely to respond to therapy. The model developed by Mitchell Gail at the NCI (National Cancer Institute) was an important step in short-term risk prediction. But while accurate for populations and good for research, the Gail model fell short for individual risk prediction. My team and I refined a fine-needle aspiration (FNA) technique so that we were able to get representative breast tissue, kind of like a "pap smear" for the breast tissue, to test for signs of precancerous change and, thereby, enabling doctors to more accurately assess a person's short-term risk of developing breast cancer and target appropriate women for prevention treatment. While this made infinite sense to us, it did not to most others. Conventional wisdom was that you did not put a needle into a woman's breast unless you had a lump or other abnormality to aim at.
We were, however, eventually able to show that for women who had a family history of breast cancer or who had prior precancerous biopsy, random sampling of her breast tissue by fine needle aspiration could more accurately predict short-term risk than by using risk models alone. In fact, women with both a five-year Gail model risk of >1.67% and who had atypical cells on their random FNA had a five-year risk of DCIS (ductal carcinoma in situ) or invasive breast cancer similar to women with BRCA1 and BRCA2 gene mutations. Once we were able to demonstrate that we could better predict which women were at high short-term risk of developing breast cancer, the challenge became to apply clinical prevention interventions. Concerns over possible side effects keep many women from using standard prevention options such as tamoxifen or raloxifene, or even prophylactic surgery. Consequently, we began early-phase testing of interventions with fewer effects using the fine needle aspiration technique to sample tissue before and after the intervention. One of our goals in developing the technique was to make the aspirations as comfortable as possible so that the patients would come back and get them again.
Briefly describe your BCRF-funded research project. What are some laboratory and/or clinical experiences that inspired your work? What are your primary goals for this research?
My first BCRF project, which is still ongoing, is developing new tissue-based biomarkers for women who are at increased risk of breast cancer but whose tissue samples obtained by fine needle aspiration did not have a high growth (or proliferation) rate even though it might have some atypical looking cells. These women are primarily post-menopausal, overweight women who are not on hormone replacement therapy. Although these women have very low proliferation rate in their benign tissue, they can still develop cancer over time. Part of the reason is that inflammatory cytokines and adipokines may promote survival and more aggressive behavior of atypical cells.
In conjunction with Dr. Stephen Hursting, another BCRF researcher at the University of Texas, we started looking at adipokines, cytokines and other inflammatory markers in breast tissue and blood. We found that we could measure the inflammation markers reliably in the breast tissue. We are currently trying to make sure that in the absence of an intervention (i.e. drugs or weight loss, etc.) that these markers are still consistently expressed over time.
Building on the first two years of our BCRF research, we have developed new pilot trials (one of which is funded by BCRF) using high-dose omega 3 fatty acids (one of which is funded by BCRF) and have proposed trials using energy balance interventions.
What other projects are you currently working on?
In general, we are interested in finding new prevention interventions that are associated with reduced side effects. There is a prevention trial funded by the NCI women who need hormone replacement therapy to control their menopause symptoms. This trial is testing an aromatase inhibitor called letrozole to see if it reduces breast tissue growth rates and the proportion of pre-cancerous cells. Another study, which will soon begin, is looking at the effects of the lignan component of flaxseed vs. placebo on tissue risk biomarkers in premenopausal women. The BCRF grants have been very helpful in that they allowed us to develop some of the biomarkers needed for these studies.
How close are we to preventing and curing all forms of breast cancer?
I don't know if I can answer that question. But at the time I completed my training in the mid-1970's, 40% or more of the women who developed breast cancer were dying of it. Now fewer than 20% of women who were undergoing regular screening at the time their breast cancer was discovered will ultimately die of their disease. Although that figure is still too high, the change over 35 years is amazing.
For prevention, we have identified drugs that will reduce by half the 5 to 10 year risk of developing breast cancer. The problem is few risk eligible women will take them. So, I think we have to look at multiple prevention strategies, emphasizing interventions likely to be attractive to women at different stages of their life. The emphasis should be on things that women can do themselves which do not require extensive medical monitoring. These interventions ideally should make them look better and feel better (like diet and exercise). We also need to give a map and a toolbox such that they can accomplish their goals. I see prevention going in that direction.
In your opinion, how has BCRF impacted breast cancer research?
BCRF has impacted breast cancer research in at least two very important ways. One is that the organization stimulates cross-collaboration by bringing together established breast cancer researchers from various fields. The collaboration between Dr. Hursting's and my group is an example of this inter-disciplinary collaboration.
BCRF also impacts breast cancer research by providing funds to researchers to allow them to quickly develop assessment tools and/or preliminary data for large projects. BCRF is unique in that it supplies funds needed to develop the clinical and translational tools needed to perform research. Having the tools and pilot data accelerates the pace of breast cancer research.
Read more about Dr. Fabian's current research projects funded by BCRF.