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11-03-23-penn-med-01-abhiram-juvvadi

Penn Medicine researchers received a $10 million grant to support clinical studies in preventing breast cancer recurrence.

Credit: Abhiram Juvvadi

A group of Penn Medicine researchers received a $10 million grant from the United States Department of Defense for their work in using a targeted drug to stop breast cancer recurrence. 

The new grant will support the current clinical studies and continued surveillance of over 200 patients who have participated in clinical studies led by the 2-PREVENT Breast Cancer Translational Center of Excellence at the Abramson Cancer Center. The grant is a part of the U.S. Department of Defense’s Multidisciplinary University Research Initiative announced in March, which awards $220 million to research studies nationwide. 

Researchers have seen promising results in initial clinical trials of a drug that suppresses breast cancer recurrence in patients by finding and targeting dormant tumor cells. Within three months, 80 percent of patients in the trial were cleared of disseminated tumor cells, which are the source of breast cancer recurrence. 

Angela DeMichele, a medical oncologist who is one of the co-directors of the Breast Cancer Translational Center of Excellence, recently presented the results of the initial trial at the European Society for Medical Oncology Congress. 

DeMichele told The Daily Pennsylvanian that — while disseminated tumor cells are usually originally found “sleeping” in the bone marrow — they can eventually travel through the bloodstream to other body parts if reactivated.

Lewis Chodosh, the other co-director of the Breast Cancer Translational Center of Excellence and chair of the Department of Cancer Biology, has been studying disseminated tumor cells and breast cancer recurrence in mice. Chodosh’s lab identified specific pathways that allow disseminated tumor cells to survive in patients and revealed promise in the possibility of drugs that could eliminate these cells completely in humans. 

DeMichele said that Chodosh’s discoveries have allowed for the lab findings to be translated into clinical research. 

“The cells have been known about for a long time…but we really didn’t understand what made the cells tick, and how you might treat them,” DeMichele said. “It wasn’t until now that we have a much better understanding of the biology of the cells and of dormancy in general, that we can start to intervene… we also have much better technologies now for detecting rare cells.”

DeMichele added the goal is not only to find these cells, but to afterwards treat patients with drugs, "specifically targeting" the sleeping cells.

Breast cancer recurrence is a lifelong issue, DeMichele said, with over thirty percent of breast cancer survivors with triple-negative, metastatic breast cancer experiencing recurrence later in life due to the awakening of dormant breast cancer cells that spread through the body.

In the four years since the study was conducted, none of the triple-negative breast cancer patients included had recurrence. To date, only two of the 51 patients who participated in the initial clinical study have experienced a breast cancer recurrence to date.

The large screening program to find individuals with these cells was launched around ten years ago. The research team screened 200 patients to find 51 that were included in the trial, at which point they went through the treatment and were then followed for a minimum of three years. 

DeMichele said it was important to follow patients who took part in the trial over several years, due to the nature of varied time of breast cancer recurrence. 

“It could be months, it could be years, it could be decades," DeMichele said. "The idea would be to continue to follow this very large group of patients to see if they relapse, to continue to test them for dormant cells and for reactivating cells."

The research team is planning to replicate the trial in a much larger patient population and has opened seven other research centers around the country. 

Forty percent of patients in the clinical trial traveled greater than 50 miles to Penn Medicine to participate, and the researchers expressed hope that the new centers will enable easier access for participants.