“The fact that we got both short-term and long-term signals of breast cancer risk suggests there may be a dynamic relationship between circulating immune cells and cancer,” said Taylor. (Photo courtesy of Steve McCaw)

Shifts in the populations of white blood cells in a woman’s bloodstream may signal a later diagnosis of breast cancer, according to a study by NIEHS researchers, published Jan. 17 in JAMA Network Open.

The study found that women with higher proportions of a white blood cell type called a B-cell experienced a higher risk of breast cancer years later. It also found that women with lower levels of another type of white blood cell, known as a monocyte, had a higher risk for developing breast cancer in the near term.

“This finding opens up a new avenue for looking at breast cancer risk,” said senior study author Jack Taylor, M.D., Ph.D., head of the NIEHS Molecular and Genetic Epidemiology Group. “Although we know a lot about how the immune system interacts with a tumor, this is one of the first studies to detail changes in circulating immune cells in the months and years before diagnosis.”

Refining risk

The new study is one of a slew of recent findings to emerge from the Sister Study, an NIEHS research initiative that enrolled women who have a biological sister with breast cancer, but did not have the disease themselves.

Jacob Kresovich, Ph.D., a postdoctoral fellow in Taylor’s lab, said previous research indicates that women with higher numbers of total white blood cells may be at higher risk of breast cancer. White blood cells are part of the immune system that protects the body against illness and disease.

Kresovich believes their findings indicate that information gained from a blood test could provide additional information about when a woman is at higher risk of developing breast cancer. (Photo courtesy of Steve McCaw)

“But white blood cells are really diverse and can be further classified based on their subtype and overall function,” said Kresovich, who is lead author of the paper. “We believed we could refine some of these associations by looking at the relationship between specific types of cells and the incidence of breast cancer.”

Timing is everything

From 53,000 women enrolled in the Sister Study, the researchers selected 2,774 participants to include in this analysis. They used a sophisticated technique called methylation cytometry to estimate the proportions of six different subtypes of white blood cells in each of the women’s blood samples.

The researchers found that the composition of white blood cell subtypes changed in the years leading up to a breast cancer diagnosis.

The proportion of monocytes, a type of white blood cell that can be activated in the presence of growing tumors, decreased in the bloodstream of women who were diagnosed with breast cancer in the year following blood draw. “Monocytes may be recruited to cancer tissue, which would explain why there would be a drop in blood shortly before the diagnosis of cancer,” said Kresovich.

Colorized scanning electron micrograph of a B-cell from a human donor. The profile of these and other white blood cells in a woman’s bloodstream may indicate future breast cancer risk. (Photo courtesy of National Institute of Allergy and Infectious Diseases)

In contrast, the proportion of B cells, which produce antibodies to fight infection and disease, was higher in women who were diagnosed four or more years later. Taylor said although the shift in the profile of these cells seems to be associated with tumors arising in the distant future, this finding needs confirmation.

“Next, we want to look more broadly at the information we can extract from these profiles and improve our predictions of who will develop cancer,” said Taylor. “We would also like to understand whether certain health behaviors alter these profiles.”

Citation: Kresovich JK, O’Brien KM, Xu Z, Weinberg CR, Sandler DP, Taylor JA. 2020. Pre-diagnostic immune cell profiles and breast cancer. JAMA Network Open 3(1):e1919536.

(Marla Broadfoot, Ph.D., is a contract writer for the NIEHS Office of Communications and Public Liaison.)