Trials target breast cancer metastasis
Breast surgeon Rebecca Aft, MD, PhD, and colleagues have spent years examining the molecular characteristics of cells responsible for metastatic breast cancer. Bringing that work into the clinical realm, she also leads clinical trials of drugs aimed at killing those cells.
Aft studies disseminated tumor cells (DTCs) — those that leave the original tumor and spread to distant sites in the body, sometimes developing into secondary tumors known as metastases. Breast tumors shed thousands of DTCs every day, and they often lodge in bone marrow.
“Bone marrow may be a DTC sanctuary, allowing DTCs to adapt and spread to different organs, where they’re a leading cause of death,” says Aft.
Her research has helped to uncover the molecular characteristics of DTCs — information that has contributed to identifying drugs aimed at killing the dangerous cells. Since 2004, she has led clinical trials testing these and other drugs in breast cancer patients at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. The scope of Aft’s work puts her squarely in the T2 stage of translational work.
In a clinical trial, Aft has studied the bone-strengthening drug zoledronic acid (Zometa®), finding that it improves survival in patients with estrogen-receptor-negative stage II and III breast cancer, prevents cancer therapy-induced bone loss and improves bone-mineral density in premenopausal women undergoing breast cancer treatment. But although zoledronic acid makes the cellular environment less hospitable for DTCs, it doesn’t kill them.
Currently, Aft is leading a study evaluating the drug trastuzumab (Herceptin®) in a specific subset of breast cancer patients: those who test positive for human epidermal growth factor receptor 2 (HER2) in bone marrow DTCs but whose tumors are HER2 negative. The 15-20 percent of breast cancer patients who fall into this category are at high risk of metastases.
Herceptin® has been shown to prevent metastasis in patients whose tumors test positive for HER2. Aft hopes her study patients also will benefit.
“Our long-term goal is to prevent metastases in women who are at high risk,” says Aft.
Early trial finds breast cancer vaccine safe
A breast cancer vaccine developed at Washington University is safe in patients with metastatic breast cancer, results of an early clinical trial indicate. Preliminary evidence also suggests that the vaccine primed the patients’ immune systems to attack tumor cells and helped slow cancer progression.
William Gillanders, MD, vice chair for research, was principal investigator of the trial. Results were reported in Clinical Cancer Research in December 2014.
The new vaccine causes the body’s immune system to home in on a protein called mammaglobin-A, found almost exclusively in breast tissue. The protein’s role in healthy tissue is unclear, but breast tumors express it at abnormally high levels. Gillanders and Washington University colleagues were the first to study the protein in breast cancer and elicit an immune response to it, then developed the vaccine based on that work. They have received funding for a larger clinical trial to test the vaccine in newly diagnosed breast cancer patients.
Highlights
- Siteman Cancer Center received an exceptional rating, the highest score possible, from the National Cancer Institute (NCI) during its five-year review in January 2015. The center’s tumor immunology program — led by William Gillanders, MD, and Robert Schreiber, PhD — also received an exceptional rating. The NCI renewed Siteman’s status as a Comprehensive Cancer Center, one of only 45 U.S. cancer centers to earn the designation for its added depth and breadth of research.
- Breast surgeon Virginia Herrmann, MD, returned to the faculty after 10 years at the Medical University of South Carolina and the Hollings Cancer Center in Charleston. She is extending Siteman’s outreach to breast cancer patients in north St. Louis County through a practice at Christian Hospital. Herrmann has met with leaders in local municipalities such as Ferguson and Black Jack to learn more about the cancer care needs of underserved patients and will work to enroll more of these patients in clinical trials.
- Amy Cyr, MD, Julie Margenthaler, MD, and co-authors reported in the Journal of Surgical Research that radiologic staging studies are overused in newly diagnosed stage I–II breast cancer patients. In these patients, routine radiologic staging in the absence of symptoms suggesting distant spread of cancer is not recommended. The study reported that 882 of 3,291 stage I-II patients underwent additional imaging and/or biopsies. Identification of distant metastasis was rare; even among these patients judged appropriate for staging, only 1.2 percent were diagnosed with metastatic disease.