Levels of a particular protein in breast cancer cells that escape the primary tumor and migrate to the bone could be an indicator of lethal cancer recurrence, according to a recent study.
doctor holding breast cancer awareness ribbon
Tests using a newly discovered protein marker ‘could further improve curative treatment of breast cancer,’ researchers say.

The process of forming secondary tumors away from the primary site is called metastasis and is responsible for the vast majority of cancer deaths.

Bone is a common destination for migrating, or metastatic, cells in breast cancer. These cells are also known as disseminated tumor cells.

Scientists already knew that the presence of disseminated tumor cells in bone marrow meant that a more aggressive form of cancer could develop. However, this does not happen in all cases. The reason for this has been something of a mystery.

Now, a collaborative study involving the Icahn School of Medicine at Mount Sinai in New York, NY, and the University Hospital of Oslo in Norway, has uncovered a potential explanation that scientists could use to more accurately assess the risk that metastatic cancer in the bone will develop in cases of breast cancer.

NR2F1 in disseminated tumor cells

In a paper that now features in the Breast Cancer Research journal, the international team describes how levels of a protein — nuclear receptor subfamily 2 group F member 1 (NR2F1) — in disseminated tumor cells in bone marrow could indicate whether the cells remain dormant or become active.

If the level of the protein is high, the cells remain dormant, if it is low, they become active and more likely to develop into a more lethal, secondary tumor.

The authors note that recent experiments have revealed that NR2F1 “plays a key role in dormancy signaling.” So, they decided to investigate its role in breast cancer that spreads to bone marrow.

Among women in the United States, breast cancer is the most common cancer and the second leading cause of cancer deaths.

According to the Centers for Disease Control and Prevention (CDC), 2015 was the latest year for statistics on breast cancer incidence in the U.S. That year there were 242,476 diagnoses of female breast cancer and 41,523 deaths to the disease.

Metastasis and NR2F1 in bone marrow

Metastasis is a complex process that involves disseminating tumor cells and follows a sequence of steps. It accounts for 90 percent of deaths associated with cancer.

The new study sought to explore the opportunity for averting breast cancer metastasis in bone by tackling disseminating tumor cells — whose biology “is poorly understood.”

The investigators analyzed levels of NR2F1 protein in bone marrow samples taken from 86 individuals with breast cancer who tested positive for disseminating tumor cells.

They found that those who had little or no NR2F1 protein in the disseminating tumor cells in their bone marrow were most likely to have a shorter survival time.

Those with high levels of NR2F1 protein in the disseminating tumor cells in their bone marrow, however, were most likely to survive for a longer time.

The researchers suggested that high levels of NR2F1 protein in the disseminating tumor cells were keeping the cells in a dormant state and contributing to the longer survival of those individuals.

‘First potential dormancy marker’

They conclude that their “bench-to-bedside work reveals the first potential dormancy marker” for how disseminating tumor cells behave.

They warn, however, that their results should be “interpreted with caution” because of the restricted number of cases that they analyzed and the differences between the individuals and their treatment.

The findings could have important implications for the treatment of breast cancer patients in the U.S. because doctors do not usually use bone marrow tests to monitor their progress.

“Tests using this protein marker,” says co-senior study author Julio A. Aguirre-Ghiso, who is a professor of medicine, hematology, and medical oncology at the Icahn School of Medicine at Mount Sinai, “could further improve curative treatment of breast cancer, sparing patients from unnecessary treatments.”

Identifying patients with disseminated disease that is not yet symptomatic and characterizing it for potential dormancy or metastatic recurrence is a game changer.”

Prof. Julio A. Aguirre-Ghiso