In aggressive form of breast cancer, response to therapy may contribute to tumor regrowth, according to Vanderbilt-led study

A recent study by a team of researchers at Vanderbilt University found that response to radiation therapy for triple negative breast cancer (TNBC)—one of the most aggressive forms of the disease—may contribute to tumor recurrence.

Marjan Rafat

Marjan Rafat, assistant professor of chemical and biomolecular engineering, explained that radiation therapy continues to be an important option for patients with TNBC because it can improve survival rates and regional control of the cancer. But in an immunosuppressed environment, radiation may increase cancer cell proliferation, said Rafat, who also holds appointments in the Departments of Biomedical Engineering and Radiation Oncology.

The study, published in the journal Biomaterials, examines changes in the extracellular matrix (ECM), the large network of proteins and other molecules that give structure to cells and tissues in the body, and how radiation affects breast cancer cell behavior in that microenvironment.

Tian Zhu

Irradiated mammary tissue showed increased fiber density compared to unirradiated controls, said Tian Zhu, the paper’s lead author and a graduate student in Rafat’s Tumor and Tissue Microenvironment Lab. “A more fibrous matrix provides a platform for cancer cells to thrive in the original tumor site.” Zhu said, adding that 3D modeling of the cellular environment was key to uncovering the novel findings. “This is the first study to quantify the effect of radiation therapy on the ECM in the breast microenvironment.”

The researchers examined irradiated mouse mammary fat pads (MFPs) and developed mammary-derived hydrogels to seed tumor cell lines into the animal models. This allowed them to assess and evaluate tumor and immune cell interactions in a preclinical model that mimics the disease process. The team includes researchers from the Vanderbilt University Medical Center, RiMED Foundation in Palermo, Italy, University of Pittsburgh, Rice University, and Iowa State University.

Zhu said next steps would include modeling on human mammary cells and tissues that could lead to realistic clinical approaches that would elevate the effectiveness of radiation therapy and minimize breast cancer recurrence.

Contact: brenda.ellis@vanderbilt.edu