Understanding How Dense Breast Tissue Leads to Cancer
Researchers at UC San Francisco have potentially discovered why women with dense breast tissue face a higher risk of developing breast cancer. Dense breast tissue poses challenges for cancer screening as it appears solid white on mammograms, complicating accurate diagnosis. According to the Mayo Clinic, this tissue not only makes detection difficult but also slightly increases the risk of cancer formation.
The new research provides insight into the mechanism underlying this risk. Dense tissue is inherently stiffer, which attracts immune cells known as macrophages to the breast. These cells release chemicals that mutate DNA, increasing the likelihood of cancerous growth. Previously, this correlation helped in the detection of cancer post-occurrence. Now, the understanding might aid in preempting the onset of cancer.
Mary-Kate Hayward, the study’s lead author, explained to Newsweek: “We’ve long known that dense breast tissue raises cancer risk, but not why. Our study demonstrates that dense tissue stiffness influences macrophages, prompting them to emit reactive chemicals harmful to nearby cells’ DNA.”
How the Study Unfolded
The research, published in Cancer Cell, aimed to find a link by examining samples from patients. By measuring tumor stiffness and using microscopic imaging of collagen, researchers discovered that stiffer tumor areas contained more collagen, scarring, macrophages, and DNA mutations.
Further analysis revealed elevated levels of STAT3, a signaling pathway implicated in cancer development, suggesting a relationship between tissue stiffness and increased macrophage presence. Experiments conducted with various gels and mouse models confirmed that a stiff environment activates STAT3 in breast cells, attracting macrophages which may support tumor growth.
Macrophages on stiff gels produce reactive oxygen species (ROS), typically associated with cancer. Although these ROS are short-lived, impairing their ability to cause distant damage, researchers found that ROS lead to oxidative damage altering fats in macrophages into DNA-damaging chemicals.
Hayward shared with Medical Xpress: “What was striking was that macrophages generated chemicals capable of traveling to nearby cells and inflicting DNA damage. We usually consider environmental chemicals as DNA-damaging and cancer-inducing, yet macrophages can produce such chemicals within the tissue.”
Subsequent experiments confirmed the findings. Dense tissue showed more macrophages, aldehydes, DNA damage, and advanced disease manifestation. Going forward, researchers aim to investigate medications that prevent aldehyde formation in macrophages.
In a statement to Newsweek, Hayward noted: “The exciting part is that this gives us something to target. If we can block these damaging chemicals, we might be able to get ahead of cancer in high-risk tissue before a tumor even has the chance to form.”