Researchers Find Dormant Breast Cancer Cells in Hiding

Scientists recently discovered how breast cancer cells are able to invade bone marrow in mice, lying dormant for an extended period of time only to resurge to create metastatic cancer relapse.

A study published in Science Translational Medicine reported how breast cancer cells that are hormone receptor-positive move through the blood and tissues within mice. These cells are searching for specific blood vessels in bone marrow that contain the E-selectin molecule.

The cancer cells have molecules on the surface that allows it to bind to E-selectin, entering into the bone’s spongy tissue, often lying dormant for years.

“Clinical studies have found that breast cancer can be caught early and treated, and patients can have no signs of disease,” said senior study author Dorothy A. Sipkins, MD, PhD. “And then 5, 10 or even 15 years later, a patient can relapse. Most often, the site of the metastasized cancer is in the bone.”

These hormone receptor-positive breast cancers are the most common form of breast cancer. Through exploitation of the body’s estrogen or progesterone, the cancer is able to grow, which results in metastatic cancer relapse.

Biopsies of bone marrow taken from human breast cancer patients have shown that roaming cancer cells — micrometastases – make their way out of the breast and into the bone marrow.

“Now we know how they are getting in,” Sipkins said. “We also identified an important mechanism that allows them to remain anchored in the bone marrow. In the mouse, our findings could offer new strategies to intervene at the molecular level before dormant cells can take hold and cause relapse.”

In order to inhibit E-selection, researchers used GMI-1271, an inhibitor currently being used in human clinical trials. The results of the study showed the compound was able to successfully stop breast cancer cells from entering bone marrow in the mice.

An additional strategy researchers tested involved administering plerixafor, which is used in bone marrow donors to push stem cells into the bloodstream to be harvested. Plerixafor forced the dormant breast cancer cells out of the bone tissue and back into circulation in the bloodstream.

This strategy was tested to help combat microscopic metastases that can spread to bone marrow before a patient is even diagnosed.

Researchers hypothesize that by pushing the dormant cancer cells back into the bloodstream, it could give the immune system, chemotherapy, or hormonal therapy another chance to kill the cancer cells.

“We are hopeful that by understanding how these breast cancer cells migrate through the body and what their life cycle is, we can discover ways to make them more vulnerable and treatable,” Sipkins said. “Our hope is to move forward with additional studies in mice to better understand our approach before moving on to studies in humans.”