Researchers at the University of Kentucky Markey Cancer Center are proposing to conduct a clinical trial that uses “avatars” to help determine the most effective chemotherapies for people with triple-negative breast cancer (BC).
Triple-negative BC is a particularly aggressive group of breast cancers that often affect younger women. Unlike receptor-positive types of BC, triple-negative cancers lack the biomarkers that oncologists use to decide which treatment a patient is most likely to respond to, making their optimal therapy a more difficult, educated guess.
“Breast cancer, we now recognize, is at least five different diseases that are completely different from each other. And the hardest nut to crack is this one called triple-negative breast cancer,” Edward Romond, PhD, an oncologist at Markey Cancer Center, said in a press release.
Since triple-negative BCs are not uniform, every patient responds to treatment in a different way. These breast cancers, however, generally responds well to chemotherapy.
Patients with triple-negative BC currently receive chemotherapy first to shrink the tumor (a process called neo-adjuvant therapy), before possibly undergoing surgery to remove as much of the tumor as possible. They are then monitored for a certain period for cancer recurrence.
Under the approach proposed by the research team, triple-negative BC patients will undergo a biopsy, and each patient’s tumorous tissue would be transferred into a mouse bred to grow human tumors, and subsequently into three dozen mice — the “avatars” — that will be divided into groups and given different chemotherapy treatments. The goal is to test which of six types of chemotherapy used to treat triple-negative breast cancers work best against a specific patient’s tumor.
Avatar work takes place while the patient undergoes neo-adjuvant chemotherapy and surgery, a process that takes about six months. Investigators hope that, by the end, oncologists will know which chemotherapy should work best for a patient, and is also most likely to reduce the risk of tumor recurrence in those patients with residual cancer after neo-adjuvant chemotherapy and, possibly, surgery.
“It would prevent us from having to experiment with each individual patient, and end up finding that they didn’t respond to that therapy,” said Kathleen O’Connor, director of Markey’s Breast Translational Group. “If we can do this, then the oncologists will no longer have to guess.”
An avatar-based approach isn’t new, she said, but not many researchers have used it to treat a patient. A key difference in this research proposal is using a trial protocol to obtain pre-treatment biopsy tissue samples to test in the avatars.
“The important thing is that we need to get the tumor tissue before they’ve been exposed to chemotherapy,” added O’Connor. “This is one of the things that make our trial unique.”
A first group of avatars treated with tissues from patient surgeries was established using pilot funding from a National Cancer Institute (NCI) designation grant. More funding is now being sought to support the collection of data, an essential step in applying for major funding to possibly move the research into clinical testing.