Meet The Researcher: Kathy Albain

Targeting stem cell biology to prevent resistance to anti-hormone therapies in breast cancer.

Kathy S. Albain, MD, is Professor of Medicine and Dean’s Scholar at Loyola University Chicago Stritch School of Medicine. As a member of the Division of Hematology/Oncology, she devotes her clinical practice to patients with breast and lung cancer at Loyola’s Cardinal Bernardin Cancer Center. She is Co-leader of the Breast Cancer Program in the Oncology Institute with Clodia Osipo, PhD, and is Director of the Breast Clinical Research Program, Co-director of the multidisciplinary Breast Oncology Center and Director of the Thoracic Oncology Program in the Cancer Center. Dr. Albain is involved in national research and advisory activities pertaining to breast and lung cancers as well as cancer survivorship and special populations research.

Drs. Albain and Osipo received their first grant from BCRF in 2013 to study a novel mechanism of resistance to anti-estrogen (endocrine) therapies driven by a growth promoting pathway called Notch. BCRF recently spoke with Dr. Albain about this study and why she chose a career in clinical research.

BCRF: How did you become interested in the Notch signaling pathway in endocrine resistance?

KA: As long as I’ve been seeing patients in the clinic I’ve been interested in trying to understand why some patients respond to treatments and others don’t. The majority of breast cancers are classified as hormone receptor-positive (ER+), that is, they express estrogen and also at times progesterone receptors. This type of breast cancer is usually initially sensitive to anti-hormonal treatment such as tamoxifen or aromatase inhibitors. However, the major hurdle to a cure is resistance to these anti-hormonal therapies, whereby the tumor regrows and then metastasizes (spreads) to other organs.

Dr. Osipo and I have been studying the Notch pathway as a mechanism for resistance to endocrine therapy for more than a decade. Our studies showed that Notch signaling promotes breast cancer stem cell production. Cancer stem cells survive endocrine treatment and can go on to metastasize. Prior to our BCRF grant, we did a pilot clinical study to look at Notch signaling as a marker of stem cell activity in breast cancers.

We're particularly interested in the activity of a type of drug called gamma secretase inhibitor (GSI) that shuts down the Notch pathway and reduces tumor size in laboratory models when combined with anti-estrogens. In our initial clinical trial – a pre-surgical ‘window’ model designed to study impact on biomarkers – women were given a GSI for seven days combined with anti-estrogens (tamoxifen or aromatase inhibitor) immediately after two weeks of anti-estrogen therapy alone.  Patients then underwent definitive surgical resection of their breast cancer. We collected biopsies at three time points: before any treatment, after the endocrine therapy alone and then at time of surgery right after the GSI treatment completed.  The aim was to see if markers of the Notch and stem cells pathways were affected by the GSI treatment. We found that this very short exposure to the drug reduced stem cell markers and increase the levels of proteins that regulate cell death. This indicates the potential of GSI to thwart resistance and kill cancer cells.  This was the first study to see if we would see similar effects in patients’ tumors as we'd seen in laboratory models, so we were very encouraged to observe a dramatic effect in a very short time span. Dr. Osipo and I are now working on finding out exactly how this Notch signaling pathway controls the cancer stem cell genes to cause resistance to standard anti-hormonal therapies and ultimately tumor recurrence. We're very excited about the possibility of combining an effective oral drug like a GSI with endocrine therapy since resistance to endocrine therapy remains a persistent clinical challenge.

Note: since this interview, Dr. Albain presented final results from this pilot clinical trial in a podium presentation at the San Antonio Breast Cancer Symposium in December 2014. The final analysis showed that multiple pathways and 18 specific genes were affected by the GSI plus endocrine therapy treatment. These included an increase in the level of three genes that regulate cell death and suppress tumor growth and a decrease in the levels of 15 genes that promote tumor cell growth and survival.

BCRF: What motivated you to pursue a career in clinical research?

KA: Well, I started my college career as a music major in pipe organ before switching to chemistry. (I am still the only chemistry major to play the organ at baccalaureate services at my college!) I loved science and became very interested in research as an undergraduate at Wheaton College. I had some wonderful mentors and I did summer research during my undergraduate studies. I thought I would be going on to graduate school in chemistry, and though I loved investigation and data analysis, I wasn't drawn to spending hours in a laboratory. Instead, I chose to go to medical school, which allowed me to apply my research and science interests in a clinical setting. Medical oncology was a field where I could do research and see patients and especially have my experience with my patients inform my research questions. My background in basic science helps me to communicate with laboratory scientists, making translational research a natural fit for me.

BCRF: On that note, can you comment on the importance of clinical/basic science collaborations in moving advances in breast cancer research to clinical management of breast cancer?

KA: We need clinical investigators and basic scientists working together to improve outcomes for our patients. These days it's hard to get funding for projects that don't combine both basic and clinical science. It’s important for the basic scientist to know that his or her research is clinically relevant, and from our side as clinical investigators, we can offer our patients some really exciting clinical trials. I find that when patients understand how participating in a clinical trial gives them a chance to play a more active role in their treatment, while advancing the field, they want to be involved.

BCRF: What do you think is the future of breast cancer? Is there a cure?

KA: There is not going to be just one cure; there are going to be many cures for different types of breast cancer. We know that ‘breast cancer’ is a complex mixture of many different subtypes defined by biologic markers measured on the tumor. The future is going to focus on tumor profiling and deep sequencing of tumor DNA and defining a menu of drugs that will be effective against specific types of tumors, tailored to the individual patient. In the metastatic setting, we will be managing the disease over an increasing life span, ultimately preventing death from breast cancer. We still have a lot to learn about micrometastases, small lesions that are not clinically detectable, and the how environment around the tumor affects tumor dormancy and recurrence. These are all very important areas of study and BCRF is supporting every one of them. All in all, breast cancer research is a very vibrant and exciting field of research and is advancing rapidly.

BCRF: What would you like our donors to know about the impact they have on researchers and scientists like yourself?

KA: BCRF is a one-of-a-kind organization that provides unique opportunities to do meaningful research that cannot be funded through traditional mechanisms. BCRF donors should understand that BCRF funds creativity, including projects like ours. We believe this is a project that could have an enormous impact on breast cancer patients and are grateful for the support of BCRF donors.