A new study from Johns Hopkins Kimmel Cancer Center has revealed that an oral bacterium commonly linked to gum disease may play a significant role in breast cancer development, particularly in individuals carrying BRCA1 gene mutations.
The research, published Jan. 15 in Cell Communication and Signaling, shows that Fusobacterium nucleatum—previously associated with colorectal and other cancers—can travel through the bloodstream, colonize breast tissue, and trigger DNA damage, inflammation, and tumor-promoting changes in cells.
Led by Dr. Dipali Sharma, professor of oncology and a John Fetting Fund for Breast Cancer Prevention investigator, the team discovered that the bacterium not only accelerates tumor growth but also enhances the spread of cancer cells from the breast to the lungs in animal models. “The key takeaway is that this oral microbe can reside in breast tissue, highlighting a connection between this pathogen and breast cancer,” Sharma said.
The study grew from earlier observational data linking periodontal disease to breast cancer. “We wanted to dig deeper and uncover the underlying biological mechanisms,” said Dr. Sheetal Parida, first author of the study.
Using both mouse models and human breast cancer cells, the researchers found that intraductal exposure to F. nucleatum led to hyperplastic and metaplastic lesions—early, noncancerous cellular changes—alongside inflammation, DNA damage, and increased cell proliferation. When introduced into the bloodstream, the bacterium accelerated growth and metastasis of established tumors.
Mechanistically, exposure to F. nucleatum induced DNA damage and activated repair pathways that are prone to errors, including nonhomologous end joining. The bacterium also increased expression of the PKcs protein, associated with enhanced tumor cell migration, invasiveness, stem-like behavior, and chemotherapy resistance.
Importantly, breast cells with BRCA1 mutations were particularly susceptible. These cells exhibited higher levels of a surface sugar, Gal-GalNAc, which facilitates bacterial binding and entry. BRCA1-mutant cells retained F. nucleatum over multiple cell generations, amplifying DNA damage and tumor-promoting effects.
“Our findings reveal a potential link between oral microbes and breast cancer risk, especially in genetically susceptible individuals,” Sharma said. “F. nucleatum may act as an environmental factor that cooperates with inherited BRCA1 mutations to drive tumor growth and aggressiveness.”
The researchers emphasized the need for further studies to evaluate the clinical significance of these findings, including whether oral health should be considered a factor in breast cancer prevention strategies.
The study was supported by the Breast Cancer Research Foundation, Congressionally Directed Medical Research Programs Department of Defense Breast Cancer Research Program grants BC191572 and BC210668, the John Fetting Fund for Breast Cancer Prevention, and the Bloomberg~Kimmel Institute for Cancer Immunotherapy.
Other contributors to the research included Deeptashree Nandi, Deepak Verma, Mingyang Yi, Ashutosh Yendi, Jessica Queen, Kathleen Gabrielson, and Cynthia Sears.
