UVA Research Reveals How Unhealthy Gut Helps Breast Cancer Spread


Discovery Could Lead to Better Treatments,
Earlier Identification

CHARLOTTESVILLE,
Va., Sept. 22, 2022 – An unhealthy gut triggers changes in
normal breast tissue that helps breast
cancer
spread to other parts of the body, new
research from UVA Cancer Center reveals.

The gut
microbiome – the collection of microbes that naturally
live inside us – can be disrupted by poor diet, long-term
antibiotic use, obesity or other factors. When this happens,
the ailing microbiome reprograms important immune cells in
healthy breast tissue, called mast cells, to facilitate
cancer’s spread, UVA Health’s new discovery
shows.

The finding could help scientists develop ways
to keep breast cancer from metastasizing (spreading to other
parts of the body). When it does, it is often deadly: Only
29% of women with metastatic breast cancer survive five
years; for men with metastatic breast cancer, that figure is
just 22%.

The discovery could also let doctors predict
which patients are at greatest risk of cancer recurrence
after treatment, the UVA scientists say.

“We show
gut commensal dysbiosis, an unhealthy and inflammatory gut
microbiome, systemically changes the mammary tissues of mice
that do not have cancer. The tissue changes enhance
infiltration of mast cells that, in the presence of a tumor,
facilitate breast tumor metastasis,” said researcher
Melanie R. Rutkowski, PhD, of UVA Cancer Center and the
University of Virginia School of Medicine. “Mast cells
recruited into the tissue environment during dysbiosis
restructure the tissue architecture in such a way that tumor
cells metastasize to other organs.”

The
Microbiome and Breast Cancer

Rutkowski has
been a pioneer in unveiling the surprising relationship
between gut health and breast cancer. Her latest work
reveals complex interactions between our gut microbes and
mast cells in the breast. Mast cells are blood cells which
help regulate the body’s immune response to disease and
allergens. Rutkowski’s new work suggests that the gut
microbiome can systemically influence mast cell behavior and
function in the presence of tumors.

Rutkowski and her
team found that an unhealthy microbiome caused the mast
cells to accumulate in the breast. These changes continued
after tumor formation in a mouse model of hormone
receptor-positive breast cancer, making the breast tissue a
prime launching ground for the cancer’s incursions into
other parts of the body.

Further, the scientists found
that the mast cells increased the amount of collagen in the
mice’s breast tissue and spurred earlier cancer spread.
Blocking the process that led to mast-cell accumulation
prevented both, significantly reducing tumor spread to the
lungs.

Based on their lab results, the researchers
examined tissue samples taken from human patients with
hormone receptor-positive breast cancer. They found these
patients, like the mice, had increased numbers of mast cells
and increased deposits of collagen. The numbers of mast
cells correlated with the amount of collagen and, notably,
the patients’ risk for a recurrence of breast
cancer.

“Mast cells have had a controversial role in
breast cancer, with some studies identifying a positive
correlation with outcome while others have identified
negative associations,” said Rutkowski, of UVA’s
Department of Microbiology, Immunology and Cancer Biology.
“Our investigation suggests that to better define the
relationship between mast cells and risk for breast tumor
metastasis, we should consider the mast cell functional
attributes, tissue collagen density and mast cell location
with respect to the tumor.”

Ultimately, she says,
doctors may be able to target the gut-mast cell relationship
in patients with breast cancer to help prevent the cancer
from recurring and spreading. They also may be able to use
the discovery to identify patients at risk for recurrence,
allowing them to tailor the treatment strategy for the
prevention of metastatic disease.

“Personalized
medicine in oncology is a promising approach to facilitate
better outcomes for patients,” said researcher Tzu-Yu
Feng, PhD, the first author of a new scientific paper
outlining the findings. “Our research on the gut-mast cell
axis has identified possible intervention points that could
be targeted for a customized approach to therapy. The
ultimate goal would be to improve survival for patients
diagnosed with breast cancer.”

Rutkowski’s
cutting-edge research is part of UVA Cancer Center’s
urgent mission to better understand and better treat cancer.
UVA is one of only 53 cancer centers in the country to be
designated as a Comprehensive Cancer Center by the National
Cancer Institute (NCI). The
designation
recognizes elite cancer centers with the
most outstanding cancer research and treatment programs in
the nation.

UVA Cancer Center is the only
Comprehensive Cancer Center in
Virginia.

Findings
Published

Rutkowski and her collaborators
have published
their findings in the scientific journal Cancer Immunology
Research
. The research team consisted of Tzu-Yu Feng,
Francesca N. Azar, Sally A. Dreger, Claire Buchta Rosean,
Mitchell T. McGinty, Audrey M. Putelo, Sree H. Kolli,
Maureen A. Carey, Stephanie Greenfield, Wesley J. Fowler,
Stephen D. Robinson and Melanie Rutkowski.

The work
was supported by Susan G. Komen, grant CCR17483602; the
National Institutes of Health’s National Cancer Institute,
grant R01CA253285; and the American Cancer Society, grant
IRG 81-001-26. Additional
support came from UVA Cancer Center, the BBSRC Institute
Strategic Programme Gut Microbes and Health, and Cancer
Research UK.

To keep up with the latest medical
research news from UVA, subscribe to the Making
of Medicine
blog at http://makingofmedicine.virginia.edu.

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