Active Research in Breast Cancer Prevention and Early Detection

Groundbreaking research is being conducted by members of the Vera Bradley Foundation for Breast Cancer Research Laboratories to prevent and detect breast cancer.

Impact of Cumulative Stress on Incidence

Breast cancer rates for African-Americans 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, doctors 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 people age, the tips become shortened making individuals more susceptible to disease and death.

Inflammation as Breast Cancer Predictor

Natascia Marino, PhD, has been comparing normal breast and cancerous breast tissue and has discovered signs of inflammation in normal tissue from people who went on to develop breast cancer. This inflammation is not present in tissue that isn’t cancerous. Dr. Marino 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. If verified, inflammation biomarkers will be identified and developed as breast cancer prediction tools.

Other Prevention and Early Detection Research

Mammogram x-rays do not see through dense tissue as well as they do through fat which may be a challenge to interpret mammograms with dense breast tissue. Additional screening tests, including digital and 3-D mammography, are in development for those with dense breasts. Unlike mammograms, none of the new tests prove to reduce the risk of dying of breast cancer. Now, Dr. Kathy Miller has recruited IU School of Medicine radiologists to join a national study evaluating a new MRI breast imaging method in individuals with dense breasts. In addition to the superior imaging, the technique can be completed in ten minutes – much faster than traditional MRI methods. The trial was approved by the National Cancer Institute in May 2017 and is enrolling patients.

Treatment of Aggressive Tumor and Recurrent Disease

The newest member of the Vera Bradley Foundation Laboratories for Breast Cancer Research, Jaeyeon Kim, PhD, is studying how people 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 the 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 like successful prevention, early detection and effective treatment.

Painful Side Effects of Treatment

Breast cancer survivors carry the burden of treatment: painful nerves and bad hearts. Bryan Schneider, MD, Milan Radovich, PhD, Kathy Miller, MD, and Lang Li, PhD, 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.

Metastatic Cancer Metamorphoses

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 a 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.

Patient Gene Signatures and Protein Markers for PI3K Inhibitors

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. 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.

Drug-Resistant Breast Cancer

Jian-Ting Zhang, PhD, 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, MD, this concept is now being directly tested in a clinical trial that started earlier this year.

Recurrence of Triple-Negative Breast Cancer

Individuals who have completed chemotherapy for triple-negative breast cancer 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, MD, 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, PhD, 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.

Activating the Immune System to Treat Triple-Negative Breast Cancer

In a nationwide clinical trial with hundreds of patient-care sites, Dr. Miller is testing a two-drug combination that activates the immune system to attack aggressive tumor cells in individuals who have the biomarker for Triple-Negative Breast Cancer recurrence. Immunotherapies activate the body’s normal cancer suppression and eradication abilities to fight cancer. Dr. Miller is senior principal investigator of the trial, partnering with a principal investigator at Vanderbilt University.