Working to eliminate recurrence in breast cancer survivors

Illustration of dormant tumor cells in breast cancer. Image credit – UPenn Medicine

CANCER DIGEST – Sept. 6, 2025 – Using repurposed FDA-approved drugs, researchers were able to eliminate residual cancer in breast cancer survivors in a clinical trial aimed at blocking recurrence. The results appear in the Sept. 5 journal Nature Medicine.

While survival continues to improve for breast cancer patients with better detection and treatment, the risk of recurrence remains a challenge for doctors. The risk varies by type of cancer and hormonal factors, with recurrence rates of 75 percent within three years for those whose breast cancers have estrogen positive receptors (ER+) and don't have receptors for HER2 (HER2-), according to City of Hope.

Recurrence is the result of dormant tumor cells, called minimal residual disease (MRD), which is measured after treatment in the blood and bone marrow samples using highly sensitive testing such as flow cytometry, which detects abnormal proteins on cell surfaces. 

In this study the researchers, led by Angela DeMichele, MD, MSCE and Lewis Chodosh, MD, PhD, tested 51 breast cancer survivors for MRD and randomly assigned them to receive either a drug called rapamycyin, hydroxychloroquine (HCQ), or a combination of both drugs. 

Rapamycin is approved as an immunosuppressant and has been shown to target a signaling mechanism that allows tumors to go undetected. Hydroxychloroquine is used to treat autoimmune diseases like rheumatoid arthritis and lupus, as well as to prevent and treat certain types of malaria.

At a median of 42 months post treatment, the patients were again tested for MRD and the results showed nearly 80 percent were clear of MRD, and three-year survival without recurrence was nearly 90 percent in the patients who received either rapamycin or HCQ, and was 100 percent for those who had received both drugs.

“Our research shows that this sleeper phase (MRD) represents an opportunity to intervene and eradicate the dormant tumor cells before they have the chance to come back as aggressive, metastatic disease,” Chodosh said in a press release. “Surprisingly, we’ve found that certain drugs that don’t work against actively growing cancers can be very effective against these sleeper cells. This tells us that the biology of dormant tumor cells is very different from active cancer cells.”

The research team is already enrolling patients in two larger ongoing studies to confirm and extend the results of this study. Both trials are available for enrollment at several cancer centers across the country. Patients interested in learning more should send email  to BreastCancerClinicalTrials@pennmedicine.upenn.edu.

Sources: UPenn Medicine press release and the journal Nature Medicine