Researchers at the Johns Hopkins Kimmel Cancer Center and the Bloomberg~Kimmel Institute for Cancer Immunotherapy have discovered that a common oral bacterium associated with periodontal disease may play a role in breast cancer initiation, tumor growth, and metastasis. The study, published Jan. 15 in Cell Communication and Signaling, highlights how Fusobacterium nucleatum—previously linked to colorectal and other cancers—can travel through the bloodstream, colonize breast tissue, and trigger inflammation and DNA damage.
Led by Dipali Sharma, Ph.D., professor of oncology and John Fetting Fund for Breast Cancer Prevention investigator, the team found that the bacterium accelerates tumor growth and promotes the spread of cancer cells from the breast to the lung in animal models of human breast cancer.
“The key takeaway is that this oral microbe can reside in breast tissue, establishing a connection between this pathogen and breast cancer,” Sharma said. She noted that the study was motivated by prior research linking periodontal disease to breast cancer risk.
First author Sheetal Parida, Ph.D., a research associate with Sharma, explained that the team aimed to uncover the underlying biological mechanisms. Using mouse models and human breast cancer cells, the researchers observed that intraductal exposure to F. nucleatum caused the formation of metaplastic and hyperplastic lesions—noncancerous changes marked by excessive cell proliferation or transformation—along with inflammation, DNA damage, and increased cell growth. When introduced into the bloodstream, the bacterium significantly accelerated tumor growth and metastasis.
The study also identified a molecular mechanism by which the bacterium promotes cancer progression. Exposure to F. nucleatum induced DNA damage and activated repair pathways prone to errors, including nonhomologous end joining, a rapid but error-prone DNA repair process. Brief exposure increased levels of a protein called PKcs, linked to enhanced tumor cell migration, invasion, stem-like behavior, and chemotherapy resistance.
Cells with BRCA1 mutations were particularly susceptible. These cells displayed higher levels of a surface sugar, Gal-GalNAc, which facilitates bacterial binding and entry. Consequently, BRCA1-mutant breast cells showed prolonged bacterial retention across multiple cell generations, amplifying DNA damage and tumor-promoting effects.
“Our findings suggest that oral microbes can influence breast cancer risk and progression, especially in genetically predisposed individuals,” Sharma said. “This points to multiple risk factors converging, with F. nucleatum acting as an environmental factor that may cooperate with inherited BRCA1 mutations to enhance breast cancer aggressiveness.”
The researchers emphasized that further studies are needed to explore the clinical implications, including whether oral health should be considered a potential risk factor for breast cancer.
Other contributors to the study include Deeptashree Nandi, Deepak Verma, Mingyang Yi, Ashutosh Yendi, Jessica Queen, Kathleen Gabrielson, and Cynthia Sears. Funding was provided by the Breast Cancer Research Foundation, the Congressionally Directed Medical Research Programs Department of Defense Breast Cancer Research Program, the John Fetting Fund for Breast Cancer Prevention, and the Bloomberg~Kimmel Institute for Cancer Immunotherapy.
