Skip to main content

Paving the way toward precision radiation oncology in breast cancer patients

By studying how tumor biology impacts response to radiation therapy, Prasanna Alluri, M.D., Ph.D., Assistant Professor, and his research team are opening new avenues for personalizing radiation treatments for breast cancer patients.

Prasanna Alluri, M.D., Ph.D.

Prasanna Alluri, M.D., Ph.D., Assistant Professor

Patients with localized breast cancer are typically treated with a systemic therapy such as hormone therapy or chemotherapy, surgery, and radiation therapy. The goal of radiation therapy in these patients is to eliminate any residual microscopic cancer in the breast and, in some cases, lymph nodes. Because radiation therapy is administered after the tumor in the breast has already been removed by surgery, assessing how each patient responds to radiation therapy is difficult. Consequently, radiation treatments in breast cancer patients are often delivered in a onesize-fits-all manner. Thus, patients with a similar stage of disease receive the same intensity and duration of treatment, even though they may exhibit wide variation in their response to radiation therapy.

In this work, which was recently published in npj Precision Oncology, Dr. Alluri and his group use preclinical models to show that the response of estrogenreceptor-positive (ER+) breast cancer to preoperative hormone therapy predicts response to radiation therapy. Thus, tumors that have undergone adaptations that make them unresponsive to hormone therapy also render them resistant to radiation treatments.

In their previous study, Dr. Alluri and his team showed that resistance to hormone therapy in ER+ positive breast cancer is mediated by BRD4, a bromodomain and extraterminal domain (BET) family protein, and that a small molecule BET inhibitor, OTX014, reverses resistance to hormone therapy. Findings for the current study show that BRD4 also mediates radiation resistance in ER+ breast cancer and that OTX015 reverses radiation resistance in these tumors. These findings could enable identification of patients who may be at higher risk of recurrence with existing treatments and support combining radiation with a BET inhibitor to reduce their recurrence risk.

“While these preclinical findings need further validation in future clinical trials, they provide a framework for developing personalized radiation treatments for ER+ breast cancer patients based on their response to hormone therapy,” Dr. Alluri says. “The fact that an experimental drug that reversed hormone therapy resistance also overcame radiation resistance in breast cancer is very exciting.”

The findings from the study and future research in this area will contribute toward the mission of the department to develop personalized radiation treatments for cancer patients.

This study was supported by a grant to Dr. Alluri from the Department of Defense’s Breast Cancer Research Program.