Metastatic Breast Cancer Clinical Trials and Research

Here are some examples of our current metastatic breast cancer research advances.

Clinical Trials

• Sara Tolaney MD, MPH, Erica Mayer, MD, and their colleagues have launched a series of clinical trials of drugs designed to stimulate the immune system to attack metastatic breast cancer. Trials of immunotherapy approaches are currently underway for all three major breast cancer subtypes (ER-positive, HER2-positive, and triple-negative).
• ER-positive breast cancer is typically treated with a combination of hormonal therapy with a targeted treatment, such as a CDK4/6 inhibitor (e.g. Ibrance, Kisqali, or Verzenio). Now, Sara Tolaney, MD, MPH, and Erica Mayer, MD, MPH, are leading clinical trials to test new ways to overcome resistance to CDK4/6 inhibitors, including combinations with immunotherapy or other targeted medications.
• A phase 2 clinical trial led by Rachel Freedman, MD, MPH, and Nancy Lin, MD, found that the combination of two oral medications — neratinib (Nerlynx) and capecitabine (Xeloda) — can be effective in patients with HER2-positive breast cancer that has spread to the brain. This is the first systemic treatment to gain recognition by the National Comprehensive Cancer Network (NCCN) guidelines for treatment of patients with brain metastases. Multiple trials are currently underway to test additional treatment approaches for cancer that has spread to the brain.

Basic Research

• Hormonal therapy, which deprives ER-positive breast cancers of estrogen, is part of after-surgery therapy for early ER-positive breast cancer and is often successful at preventing return of the disease. However, ER-positive breast cancer can recur many years later, often at a site far from the original tumor. Researchers led by Myles Brown, MD, have discovered that breast tumor cells can carry an abnormal "receptor" for estrogen, potentially allowing them to grow even when estrogen is absent. Researchers hope to use this finding to guide the development of new drug agents.
• Brown and his colleague Rinath Jeselsohn, MD, are studying a particularly promising class of drugs for metastatic, ER-positive breast cancers. Known as selective estrogen receptor degraders (or SERDs), they clamp onto the estrogen receptor and cause it to crumble, so the tumor cells no longer respond to estrogen.
• Other research is focusing on the molecular makeup of breast tumors — the presence of genetically distinct cells within a single tumor. Tumors with the most "heterogeneity" — the greatest diversity of cell types within them — are often more likely to resist treatment and to metastasize. Researchers led by Kornelia Polyak, MD, PhD, have discovered that the fastest-proliferating cells within a tumor aren't necessarily the main drivers of tumor growth, suggesting that efforts to develop new drugs should focus on targeting the actual driver cells.
• Up to 50 percent of HER2-positive breast cancers spread to the brain, but scientists have known little about how the process occurs. Recently a team of researchers including Nikhil Wagle, MD, Eric Winer, MD, Ian Krop, MD, PhD, Jean Zhao, PhD, Nancy Lin, MD, and Shom Goel, MD, PhD, found that approximately 12 percent of such tumors contain mutations that may explain why they don't respond well to the target drug trastuzumab, also known as Herceptin. Researchers in Zhao's lab have implanted patients' metastatic tissue into animal research models, making it possible to test various drugs to see which may be most effective against the disease.