A groundbreaking clinical trial demonstrates the potential to pinpoint breast cancer survivors at elevated risk of recurrence due to dormant cancer cells. Moreover, these cells can be effectively targeted using repurposed, existing medications. The study, spearheaded by researchers at the Abramson Cancer Centre of the University of Pennsylvania and Penn’s Perelman School of Medicine, was published in Nature Medicine.

Although breast cancer survival rates are improving due to advancements in detection and treatment, relapses still occur. These recurrences, arising from dormant cancer cells that evade initial therapies, pose a meaningful challenge. The CLEVER trial, a Phase II study, explored whether eradicating these dormant cells could lower the risk of breast cancer returning.

“The CLEVER study is the first randomized trial designed to target dormant tumor cells to prevent breast cancer recurrence,” said Dr. Angelo DeMichele, the Jill Abramson Endowed Professor in Breast Cancer Excellence at Penn’s Perelman School of Medicine, and the study’s lead author.”These results suggest that we’re on the right track.”

CLEVER trial Details and Ongoing studies

“These results suggest that we’re on the right track.”

The CLEVER trial involved 129 patients with hormone receptor-positive, HER2-negative breast cancer who had completed standard treatments like chemotherapy, surgery, and radiation. These patients exhibited evidence of dormant tumor cells, detected through a biomarker called Ki67, following treatment with an aromatase inhibitor.

Participants were randomly assigned to receive either two years of low-dose chemotherapy (methotrexate and capecitabine) or continued endocrine therapy alone. The results revealed a notable decrease in the risk of recurrence among those who received low-dose chemotherapy. Specifically, after three years, 89% of patients in the chemotherapy group remained recurrence-free, compared to 74.2% in the endocrine therapy group.

“these results suggest that targeting dormant tumor cells can reduce the risk of breast cancer recurrence,” said Dr. DeMichele. “The findings also highlight the importance of identifying patients who are most likely to benefit from this approach.”

To further validate these findings, the research team is currently enrolling patients in two larger, ongoing studies: the Phase II ABBY clinical trial and the Phase II PALAVY clinical trial, both accessible at various cancer centers nationwide.

Dr. DeMichele previously presented interim data from the CLEVER study at the European Society for Medical Oncology (ESMO) Congress 2023.