Vera Bradley Foundation for Breast Cancer Discoveries
Funding generated by the Vera Bradley Foundation has resulted in the recruitment and retention of 34 researchers who work together to discover the ways cancer grows, develop ways to block its progress and deliver new treatments to women.
The Indiana University Melvin and Bren Simon Cancer Center’s breast cancer research program is recognized by the National Cancer Institute for meeting rigorous criteria for world-class, state-of-the-art multidisciplinary cancer research, and it offers the only place in Indiana that introduces first-to-human drugs into treatment. Thousands of generous donors, volunteers and the Vera Bradley Company have shared the vision and passion of Pat Miller and Barbara Baekgaard, co-founders of Vera Bradley, and have worked to bolster the breast program since the foundation was formed in 1999.
According to Patrick Loehrer, M.D., director of the IU Simon Cancer Center, members of the Vera Bradley Foundation for Breast Cancer Research Laboratories receive much of the seed funding for their research from the support the foundation provides. These critical donations allow them to continue to act on original ideas and generate important data to prove their viability. One million dollars in seed funding from the Vera Bradley Foundation generates $10 million in scientific research funding.
Here is a snapshot of some of the groundbreaking research being conducted by members of the Vera Bradley Foundation for Breast Cancer Research Laboratories.
Prevention and Early Detection
Breast cancer rates for African-American women are greater than in Caucasian women, especially for aggressive types of breast cancer. Might social and physical stresses play a role? To investigate the possibility, Drs. Brittney-Shea Herbert, Anna Maria Storniolo and Hiromi Tanaka, along with behavioral and social scientists, are deploying a questionnaire to explore the correlation of cumulative stress (emotional or physical) to telomere length. Telomere length is an indicator of both stress and the onset of breast cancer. Telomeres are caps on the tips of chromosomes that preserve genetic integrity. As we age, the tips become shortened making us more susceptible to disease and death.
Natascia Marino, Ph.D., has been comparing normal breast and cancerous breast tissue and has discovered signs of inflammation in normal tissue from women who went on to develop breast cancer. This inflammation is not present in tissue that isn’t cancerous. She is excited by this finding and is working to validate it. In a separate study, the Nakshatri Laboratory is comparing normal, tumor-adjacent normal and tumor tissues, and its scientists have observed inflammatory changes in breast tissue adjacent to the tumor. Future studies will focus on validating the presence of inflammation followed. If verified, inflammation biomarkers will be identified and developed as breast cancer prediction tools.
Mammogram X-rays do not penetrate — or "see through" — dense tissues as well as they do through fat. And it means it may be a challenge to interpret mammograms for women with dense breast tissue. Additional screening tests, including digital and 3-D mammography, are in development for women with dense breasts. Unlike mammograms, though, none of the new tests is proved to reduce the risk of dying of breast cancer. Now, Dr. Kathy Miller has recruited IU radiologists to join a national study evaluating a new MRI breast imaging method in women with dense breasts. In addition to the superior imaging, the technique can be completed in 10 minutes – much faster than traditional MRI methods. The trial was just approved by the National Cancer Institute in May and will begin to enroll patients in the next 4 to 6 weeks.
Treatment of aggressive tumor and recurrent disease
The newest member of the Vera Bradley Foundation Laboratories for Breast Cancer Research, Jaeyeon Kim, Ph.D., is studying how women carrying hereditary BRCA mutations are prone to high-grade ovarian and triple-negative breast cancers. He developed a mouse model that offers a unique opportunity to deepen our molecular understanding of these equally dreaded diseases. In particular, he anticipates that learning about cancer initiation and early progression will be very helpful on many fronts: successful prevention, early detection, and effective treatment.
Breast cancer survivors carry the burden of treatment: painful nerves and bad hearts. Bryan Schneider, M.D., Milan Radovich, Ph.D., Kathy Miller, M.D., and Lang Li, Ph.D., recently discovered a biomarker that will identify patients who may develop toxicity to taxane, one of the commonly used chemotherapies. This is the first step in preventing these painful and life-threatening side effects of treatment.
Early-stage tumors are biologically complex; however, once tumors metastasize to other organs, the complexity of the burgeoning cancer “system” is extraordinary. Drs. Hari Nakshatri, Ken Nephew, Lang Li, Yunlong Liu and Kathy Miller want to understand why breast cancer cells that spread to the liver and brain start acting less like breast cells and more like cells in their new environment. They are engineering these complex interactions and changes using computational and mathematical modeling. Their goal is to understand the metamorphoses that take place so that treatment can effectively target the process.
Treatments work best when drugs attach to biomarkers and kill complex breast cancer tumors. In the new era of personalized medicine, this is the goal, but we’re not there yet. For instance, a new class of drugs called PI3K inhibitors was developed for estrogen positive (ER+) breast cancers; yet, patient response to this targeted drug has been disappointing. Drs. Hari Nakshatri and Sunil Badve have discovered a new gene signature and protein markers that can further define patients who may benefit from these drugs. Adding this important information and developing a new clinical trial is now under way.
Jian-Ting Zhang, Ph.D., has discovered a metabolic process that is awry in breast cancer cells that have become resistant to drug therapy. He has also found that a commonly used class of antacids – proton pump inhibitors – stabilize cell metabolism, thereby maintaining the drug’s effectiveness. In collaboration with Kathy Miller, M.D., this concept is now being directly tested in a clinical trial that started earlier this year.
Women who have completed chemotherapy for triple-negative breast cancer (TNBC) and have residual tumor in their breast and lymph nodes at the time of surgery have a high risk for recurrence of the disease within 18 months. Kathy Miller, M.D., developed the first clinical trial in the world to intervene during remission to give therapy with the potential to reduce recurrence. With this trial concluded, she and Milan Radovich, Ph.D., have identified the subsets of patients who did well and remain cancer free to determine biomarkers for survival. They have also identified blood-based biomarkers of those who recurred quickly. While those biomarkers may predict recurrence, the same biomarker could identify cancers before diagnosis. Drs. Radovich and Miller plan to evaluate the biomarker in a nationwide screening study expected to start later this year.
In a separate nationwide clinical trial with hundreds of patient-care sites, Dr. Miller is now testing a two-drug combination that activates the immune system to attack aggressive tumor cells in women who have the biomarker for TNBC recurrence. Immunotherapies activate the body’s normal cancer suppression and eradication abilities to fight cancer. She is senior principal investigator of the trial, partnering with a principal investigator at Vanderbilt University.
She is also testing two chemotherapy agents in women with TNBC and a high risk of recurrence. The trial includes a specific biomarker likely to predict which chemotherapy will be the most effective for individual patients. She is senior principal investigator of the trial, partnering with a principal investigator at Vanderbilt.
Drs. Bryan Schneider, Anna Maria Storniolo, and Kathy Miller joined with colleagues at the Fox Chase Cancer Center to conduct two clinical trials evaluating novel immunotherapies in women with aggressive breast cancer. These trials incorporate evaluation of biomarkers so we will learn who benefits from this important therapy.
Drug and New Product Development
Vera Bradley Foundation breast cancer researchers are partnering with Broad Institute of MIT and with Harvard University to develop a comprehensive map of the genome and proteome of the normal breast. This new resource will help researchers worldwide to understand cancer-specific differences in proteins involved in the development of breast cancer. Proteins found in breast tumors will be compared with proteins in normal breast tissue to discern the differences. Proteins important in the development of disease will become biomarkers to detect early disease and aid in drug discovery.
Samy Meroueh, Ph.D., is interested in developing new therapeutic agents to prevent or reverse cancer metastasis. His laboratory has discovered the first inhibitors of uPAR, a receptor that is only expressed in cancer cells that are prone to spread to distant organs. Recently, Dr. Meroueh has discovered a small molecule that inhibits breast cancer cell invasion and bone colonization. His compounds stops metastasis in laboratory models by directly targeting the malignant cells. Dr. Meroueh is currently pursuing these novel small molecules in animals to evaluate their ability to prevent and inhibit bone metastasis.
Milan Radovich, Ph.D., who is an expert in the genetic analysis of cancer, has embarked on an international research project. He is collaborating with researchers at Purdue University and the University of Texas rto develop a device to detect TNBC biomarkers in African women who are at high risk for this disease. His goal is to develop a low-cost and portable method for breast cancer detection appropriate to test in Kenya where health access and resources are scarce. Ultimately, the device could be utilized in U.S. public hospitals and become a routine screening device in all clinics.