Researchers Look at Ways to Target Early Breast Cancer Progression

Newswise — Fariba Behbod, PharmD, PhD, has received a $930,000 grant from the U.S. Department of Defense to study a new targeted therapy option for people diagnosed with ductal carcinoma in situ (DCIS).

Before breast tumors become invasive, they often start as a condition called DCIS. DCIS is found in about one in every five new breast cancer cases. Typically, DCIS patients undergo aggressive treatments like surgery and radiation. However, only about half of untreated patients will actually develop invasive cancer. In this study led by Dr. Behbod, professor in the department of Pathology and Laboratory Medicine, the main goals are to identify which cases of DCIS are likely to become invasive and treat them appropriately.

“Our research suggests that ‘bad’ DCIS cases, which are more likely to become invasive, have higher levels of a protein called NRAS,” Dr. Behbod said. “This protein is known to drive various types of cancer.”

Dr. Behbod added that even though most DCIS cases are estrogen receptor-positive and have low cell growth rates, high levels of NRAS can turn them into an aggressive form of breast cancer known as basal-like breast cancer, which is estrogen receptor-negative and grows rapidly. NRAS triggers this transition by activating another protein called JAK2, which can be targeted by drugs. In a pilot study led by Dr. Behbod, researchers examined a small cohort of DCIS patients consisting of those who progressed versus those who did not. Their results suggest that high levels of NRAS can identify the 25 to 50% subset of cases who may progress, unless treated by the proposed therapy targeting the NRAS pathway. This contrasts the current strategy in which all DCIS patients generally undergo aggressive treatments.

Building on their initial findings, Dr. Behbod will use animal models to confirm the role of NRAS in causing basal-like breast cancer. Then, using animal models, they will see if blocking the NRAS-JAK2 pathway, with a drug called ruxolitinib, can stop the progression of DCIS. Ruxolitinib is already approved by the Food and Drug Administration to treat myelofibrosis.

“It is common for breast cancer patients to begin their journey with a DCIS diagnosis,” Dr. Behbod said. “We hope this study will provide a new targeted therapy option to halt the development of an aggressive subtype of invasive breast cancer at its earliest stage.”