Breast cancer is the most commonly diagnosed cancer in women, yet one of its most intriguing features remains unexplained: the disease does not occur evenly across adulthood. Instead, breast cancer incidence rises sharply at two distinct ages—around 45 and 65 years—even within the same tumor subtypes. Why these two windows exist has puzzled researchers for decades. Rather than reflecting chance or hormone status alone, emerging evidence suggests that the breast itself may undergo distinct phases of biological aging that temporarily increase its vulnerability to cancer. If these periods of heightened susceptibility can be understood, they could fundamentally change how breast cancer risk is assessed. Uncovering the biological basis of these age-related “windows of opportunity” could reveal why some women develop cancer while others do not, and open new avenues for earlier detection and prevention.
This project will investigate whether cyclical changes in breast aging create temporary states that favor tumor initiation. Combining novel mouse models with human breast cancer datasets, the research team will examine how the cancer-driving protein MYC reshapes RNA splicing—a fundamental process that determines how genes are translated into functional proteins—during different stages of aging. They will also characterize changes in the breast tissue microenvironment, including the extracellular matrix, and determine whether these aging-associated molecular signatures are shared across genetically diverse models with different cancer susceptibility. Finally, the team will search for protein markers in blood that reflect these cyclical aging states and evaluate whether they distinguish women with breast cancer from healthy individuals. Together, these studies could lay the foundation for a new generation of blood-based risk prediction tools and identify biological pathways that can be targeted to prevent breast cancer before it develops.