Kathy D. Miller, MD :: Profile
Indiana University School of Medicine, Indianapolis, IN
Tell us a little about yourself and how you became interested in breast cancer research.
I first became interested in cancer as a second-year medical student. I was fascinated by the biology and power of cancer; imagine a single cell that escapes the normal control of growth and aging to become lethal. I spent that following summer doing basic cancer research. My laboratory mentor took me on rounds and to his clinic. In no time, I was hooked. I was struck by the impact of breast cancer on our patients (and their families) lives. A colleague likens this to the impact of the 9/11 attack; suddenly life changes and it seems like there is no safe place in the world. But I also saw that women are resilient and frequently emerge as stronger versions of their former selves. I discovered that I enjoyed taking care of the women with breast cancer, whether the news called for laughter or tears. And I was determined to focus my research on decreasing the need for tears.
Briefly describe your research project.
BCRF funding has allowed me to pursue several projects that might otherwise not have been possible.
1) A monumental change is underway in how we think about and treat breast cancer. In the past we concentrated on anatomic features like the size and location of the tumor masses and the appearance of the cells under the microscope. Now biology and chemistry dominate our thinking because these are the reasons that cancers behave as they do. Anatomy is still important, but our first questions now focus on the 'character' or 'biology' of the tumor. Women have long understood that 'one size NEVER fits all.' That's true in breast cancer therapy as well. My first BCRF project collected blood and tumor samples to determine the gene and protein 'fingerprints.' We compared the fingerprints of patients who benefited from treatment to the fingerprints of those whose tumors were resistant. This work will allow us to individualize therapy for future patients.
2) My interest in angiogenesis has fostered ongoing productive collaborations with members of the Department of Imaging Science, Drs. Gary Hutchins and Qi-Huang Zheng. Our long-range goal is to develop noninvasive imaging techniques that will enhance knowledge of breast cancer biology and guide therapy with antiangiogenic agents. Imagine taking a small 'test dose' of therapy and using special x-rays to determine if your breast cancer will respond to that treatment. BCRF funds development of new imaging techniques and laboratory studies, as well as our first pilot clinical trial.
3) BCRF (through grants to the Eastern Cooperative Oncology Group) has funded studies on the blood, urine and tumor samples collected from patients enrolled in the E2100 trial that I led. E2100 was the first phase III trial to prove the benefit of antiangiogenic therapy in women with advanced breast cancer, reporting the largest improvement in progression free survival to date. The laboratory data that formed the basis for E2100 was partly funded by BCRF. Now we hope these correlative studies will help us predict which patients will benefit most from this treatment.
4) BCRF is currently funding a phase II trial based on laboratory data from Dr. Pat Steeg at NCI. Preliminary data suggest that an old drug, medroxyprogesterone acetate (MPA), inhibits two critical features of cancer - metastasis and angiogenesis - in estrogen (ER) and progesterone (PR) receptor negative breast cancers. The trial includes both clinical and biologic endpoints to maximize the information gained.
Q.What are your primary goals for this research?
Advances in breast cancer treatment require new therapeutic strategies that are firmly rooted in an understanding of biology. As such, the major goal of my research is to evaluate innovative biologically based therapies in translational trials that yield both clinical and laboratory data. To put it more simply, my goal is to be a two-way bridge between the laboratory and clinic ï¿½ bringing basic advances to the clinic and trying to understand our clinical observations in the lab.
The Breast Program at Indiana University has focused on angiogenesis (the growth of new blood vessels into a tumor) and antiangiogenic therapy (how we can stop the growth of those blood vessels) for over a decade. This focus spans departmental boundaries and has taken several forms: laboratory evaluation of the anti-angiogenic activity of new and established drugs, imaging modalities that measure the tumor's blood vessels, clinical trials of anti-angiogenic agents, and studying how inherited differences in the genes that control blood vessel growth might influence the risk of developing breast cancer and likelihood of response to treatment.
Who do you think will benefit from your research?
I treat a large number of patients, many of whom have benefited personally by taking part in BCRF funded research. But good research reaches far beyond the walls of my clinic. Patients elsewhere, both now and in the future, benefit from the 'standard' therapies that were first studied thanks to BCRF.
How has your research focus changed since your first BCRF grant, and how would you say that our grants have had an impact on your work and the field?
The cornerstone of my research focus - facilitating an interplay between the laboratory and the clinic - has remained constant. As laboratory scientists may advances, our clinical trials follow (and occasionally lead). In some areas BCRF has allowed us to pursue small pilot studies and obtain data crucial to obtaining continued funding. In other projects, BCRF funding has allowed us to expand the knowledge gained from a larger project. For example, the E2100 trial was supported by NCI but we would have had no funding for the important blood and tissue studies without BCRF.
How close do you think we are to preventing or finding a cure for breast cancer?
We already have many cures for breast cancer; surgery (with or without radiation) cures many women. Hormonal therapy, chemotherapy, and now herceptin cure even more. BUT our current therapies don't work for everyone, and can have troubling (at times life-threatening) side effects. Research clearly tells us that breast cancer isn't one disease. We need to find more cures, with fewer side effects. Equally importantly, we need to match the right cure to the right patient to minimize the harm our therapies can cause. The pace of progress has never been quicker and is never quick enough.
Read more about Dr. Miller's research projects funded by BCRF.