Dr. Vered Stearns has dedicated her career to finding ways to improve current therapies by individualizing strategies for the treatment and prevention of breast cancer. These strategies have evolved over the years to include many different options for a more personalized approach. The use of biomarkers as a tool to predict risk of breast cancer or response to treatment is an area of research where Dr. Stearns and her BCRF colleagues have made significant contributions.
As Dr. Stearns explains, a common misperception is that all breast cancers are the same. We know now that, in fact, every breast cancer is unique. Individual tumor cells within a breast cancer can respond very differently to the same treatment. However, a deeper understanding of tumor biomarkers can help us create a more personalized approach to cancer treatment.
She describes tumor biomarkers as genes, proteins or molecules in tissue or blood that can be informative about a patient’s individual risk or response to treatment. Identifying biomarkers may help us to identify when a patient is likely to have a recurrence of breast cancer or if a specific treatment will be beneficial for one individual but make no difference for another—potentially alleviating the burden of unsuccessful treatment, over-treatment and exposure to side effects associated with some therapies.
Dr. Stearns’s team is currently studying how a specific weight loss intervention may affect biomarkers that can predict the risk of breast cancer recurrence.
BCRF recently spoke with Dr. Stearns about her research, as well as her experience as a member of the BCRF Scientific Advisory Board.
BCRF: How did you become interested in breast cancer research? Did you ever consider a different career?
Dr. Stearns: I decided at a very young age that I wanted to be a physician and was fascinated by molecular biology and genetics. I was initially drawn to the field of pediatric leukemia, particularly because of the many advances in treatments and improved outcomes in this form of cancer. During medical school I became very interested in internal medicine and was fortunate in my fellowship and early career to work with some well-known breast cancer oncologists including Daniel Hayes, Marc Lippman and Nancy Davidson who inspired me to pursue breast cancer research. And I never looked back.
BCRF: What inspired your current BCRF project? What are your primary goals for this research?
Dr. Stearns: Since very early in my research training, I have been interested in developing more personalized approaches to both treatment and prevention of breast cancer. Over the last decade my BCRF research has evolved but has always been focused on identifying biomarkers to help us predict who is at risk for breast cancer and identify interventions to reduce that risk. In our trials, we use the healthy (contralateral) breast of women who have had breast cancer as a high risk model and look for biomarkers that change in response to an intervention. Using this model, we’ve studied the effects of aromatase inhibitors and statins and more recently, initiated a weight loss intervention that was developed at Johns Hopkins University for individuals at risk of cardiovascular disease (CVD). In studies for prevention of CVD, my Johns Hopkins colleagues compared two strategies for effective weight loss: an in-person intervention and a remote (phone or internet-based) intervention and showed that the interventions were equally effective.
As you know, being overweight or obese is also associated with worse breast cancer outcomes, so we were interested in testing whether the remote weight loss intervention tool could help our breast cancer patients achieve a healthy weight. In the process, we wanted to know if weight loss would have an effect on biomarkers, such as inflammatory molecules and changes in gene regulation that we could measure in blood or in the healthy contralateral breast of our breast cancer patients. Our hope is that we can identify biomarkers that can predict the risk of breast cancer recurrence and study whether successful weight loss can change the levels of those biomarkers and thereby reduce the risk of recurrence. We also hope to use the biomarkers to inform us who will benefit from a relatively straight forward weight loss intervention and who may need additional approaches.
BCRF: Are there specific scientific developments and/or technologies that have made your work possible? What additional advancements can help to enhance your progress?
Dr. Stearns: The internet and smart phone technology are important components of our current study. They allow us to remain in contact with our study participants, to monitor their eating and activity levels, and to coach them in order to improve their success rate. Patients can log their day-to-day quality of life and other patient-reported measures without having to travel to the clinic or meet with our study staff. This allows them to participate in the trial while maintaining their usual daily activities.
Another advance is our ability to use a small amount of tissue or blood to measure changes in multiple genes and proteins at one time. This will help us to not only monitor disease, but also identify personalized treatment interventions. The development of liquid biopsy technology is an exciting innovation that could replace or reduce the need for tissue biopsy. My colleague Ben Park will be starting a study through the Translational Breast Cancer Research Consortium to measure tumor DNA in the blood of breast cancer patients during pre-surgical treatment (neoadjuvant therapy) to see if this is could be a reliable method to measure response.
Note : To read more about liquid biopsy, read our recent interview with Dr. Park.
BCRF: What exciting trends do you see emerging in breast cancer research in the next five years?
Dr. Stearns: There are many areas of research that I am excited about. In particular, new technologies will allow us to study more carefully tumors from individual patients and enhance our ability to provide individualized treatment recommendations. There is a lot of excitement around the future of immunotherapy for breast cancer. At the 2015 annual meeting of the American Association for Cancer Research, my BCRF colleague, Leisha Emens reported some promising results with an immune checkpoint inhibitor in triple negative breast cancer. One of the challenges in immunotherapy for breast cancer, however, is that many breast cancers do not cause an immune response and this limits the effectiveness of these treatments. We believe that this may be due in part to suppression of genes regulating the immune system by a process called gene methylation. Unlike gene mutations that cause permanent changes to the genes, methylation of genes can be reversed. Our group has always been interested in this field (called epigenetics, the study of non-inherited gene regulation) and my colleague Roisin Connolly and our team are looking at a targeted therapy using histone deacetylase (HDAC) inhibitors that can reverse gene methylation and restore normal gene function. We are particularly interested in using HDAC inhibitors to restore expression of genes that regulate immune response to see if we can improve the effect of immune-based drugs in breast cancer.
In addition, there is also a lot of work being done to understand the underlying biology of obesity and breast cancer risk. Of course, Clifford Hudis and his colleagues are working hard in this area and have made some exciting progress that could help us identify normal weight women who might be at increased risk.
BCRF: Tell us about the upcoming book on novel biomarkers that you conceived and for which you are editor-in-chief. Why is this an important subject?
Dr. Stearns: I’ve always been interested in individualizing treatment and prevention approaches for breast cancer. As editor of the Springer volume on Novel Biomarkers, part of a new BCRF series, I invited BCRF colleagues who are using biomarkers to individualize treatment, to write specific chapters related to their expertise. The volume will include topics on biomarkers of risk and prevention and response to treatments, such as radiation and endocrine therapies. We will also cover the use of new technologies for biomarker discovery and monitoring, including circulating tumor cells and tumor DNA, and tumor metabolomics – the study of how tumors utilize energy.
We know that tumor heterogeneity is a big challenge in the treatment of breast cancer.
Not only is every breast cancer unique, but even individual tumor cells within a breast cancer can respond very differently to the same treatment.
The Springer volume really focuses on what we’ve learned about biomarkers and ways we can utilize a variety of biomarkers to find the best treatment for each patient. It’s been an exciting project and wonderful opportunity to work with some of my BCRF colleagues.
This is an important subject because tumor biomarkers may help us to identify with a high level of certainty whose breast cancer is likely to come back or who will benefit from a specific treatment versus those who will not, so that treatments can be adjusted based on individualized risk assessment. This will reduce over-treatment and exposure to side effects associated with some therapies, as well as reduce patient and health care costs by not treating a patient with drugs that may not work.
I’m excited about the role that tumor biomarkers will play in helping us individualize treatments in the future, so patients are getting the right treatment at the right time.
BCRF: Tell us about your experience as a member of the BCRF Scientific Advisory Board.
Dr. Stearns: It has been an extraordinary honor to serve as a member of the BCRF Scientific Advisory Board (SAB) and to work with some of the giants in the field. It has expanded my perspective beyond my personal experience as a translational researcher, to better understand the potential of new technologies and approaches to the treatment and prevention of breast cancer. What has impressed me most, as both a grantee and member of the SAB, is the approach that BCRF takes in identifying investigators and projects most likely to advance the field and giving investigators the freedom to pursue their best ideas, rather than restrict them to a narrow focus outlined in a list of specific aims. This approach continues to fuel the field at a time when federal funding is becoming more and more difficult for scientists at any career level to obtain. At every national meeting and in every major breakthrough in breast cancer, you hear about the work of BCRF grantees. This clearly speaks to the success of BCRF’s approach in identifying the most promising scientists and projects and its impact on improving patient outcomes. The work of BCRF and its researchers has changed and will continue to change the face of breast cancer.
BCRF: What does the end of breast cancer look like to you?
Dr. Stearns: I’m still hopeful that we’ll have many different cures for breast cancer as we identify new biomarkers and come up with novel treatments for more personalized therapies.
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