PHILADELPHIA — Penn researchers have found that a combination of common, generic drugs could be used to kill dormant breast cancer cells, preventing the disease from recurring.

Though often highly treatable, breast cancer returns in about 30% of patients and is then almost always fatal.

Relapse can happen at any time — months, years or decades after initial treatment — when cancer cells that have been essentially hibernating in other parts of the body “wake up” and begin rapidly multiplying again.

Now Penn researchers believe they have developed a test to identify people who have dormant cancer cells and a drug regimen to kill those cells before they are able to turn into cancer.

In an ongoing clinical trial, patients periodically had their bone marrow tested for the presence of dormant cancer cells. Those who tested positive for dormant cancer cells received a combination of two repurposed drugs — hydroxychloroquine, an anti-malaria drug used to treat autoimmune diseases, and everolimus, which prevents organ rejection after a transplant.

The drugs cleared dormant cancer cells from 80% of the 51 breast cancer patients who participated in the study.

Three years later, 90% who received one drug remained cancer-free, as did 100% of those who received both drugs, according to findings published in the journal Nature Medicine earlier this month.

The work was supported by a $10 million federal grant.

The findings are early results that must be confirmed in larger studies before doctors could even consider making treatment available to the public.

But the technique is promising for thousands of patients who live in constant fear that their cancer will one day return, said Angie DeMichele, the codirector of the breast cancer research program at Penn’s Abramson Cancer Center.

“Right now, we just don’t know when or if someone’s cancer will come back — that’s the problem we set out to solve,” she said.

Study participants told The Inquirer in 2023 that the trial had helped them to live their lives without constant anxiety and fear of their cancer returning.

The next steps will be larger clinical trials and ongoing monitoring of past participants.

Finding hidden cancer cells

After treatment, it’s common for some breast cancer cells to go dormant, and settle in other parts of the body, without multiplying. DeMichele likens the phenomenon to bears hibernating — their metabolism slows down and they rely on stores of energy for months.

Once dormant cancer cells reactivate and begin multiplying rapidly again, they are nearly impossible to treat because they have spread to the bones and other organs, such as the liver. Researchers set out to find the dormant cancer cells with the goal of eliminating them before they could wake up.

Dormant cancer cells are difficult to locate because they don’t rapidly multiply like most cancer cells and therefore do not show up on regular scans. But doctors have long known that dormant cancer cells often settle in bone marrow, the spongy center of bones where red blood cells are made.

The Penn trial found that they could identify patients who had dormant cancer cells — and were therefore at greater risk of their cancer recurring — by periodically testing their bone marrow.

Those whose bone marrow tests showed that dormant cancer cells were present received six cycles of one or both of the repurposed drugs.

Researchers selected drugs that were known to target cells’ metabolism and ability to multiply.

One of the drugs, hydroxychloroquine, was pushed by President Donald Trump as a treatment for COVID-19, despite scant evidence that it was an effective or safe treatment for the virus.

DeMichele stressed that researchers will need to test the medication combination among many more patients in larger trials before they can recommend it as a treatment for dormant breast cancer cells.

Two study participants have had a cancer recurrence, representing a 4% recurrence rate after 3 ½ years.

Researchers estimated that about 30% would have seen their cancer return if they had not participated in the study and instead received currently available treatment.

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