DCIS Cell Atlas Reveals Clues to Invasive Breast Cancer Progression

Researchers at The University of Texas MD Anderson Cancer Center have developed an in-depth map of the tumor microenvironment surrounding estrogen receptor-positive ductal carcinoma in situ (DCIS), the most prevalent form of preinvasive breast cancer. This atlas, created by studying samples from normal breast tissue, DCIS, and invasive breast cancers, may clarify why some DCIS lesions develop into invasive breast cancer while others do not, and could aid in improving risk prediction and developing targeted treatments for those at higher risk.

Dr. Nicholas Navin, co-lead of the study, explained that DCIS is a snapshot of preinvasive breast cancer, but not all cases progress, highlighting the complexity of the biology involved. Dr. Savitri Krishnamurthy, co-lead and professor of Anatomical Pathology, emphasized that the atlas unveils the surrounding cells and structures that could facilitate disease invasion.

The team reported their findings in Science, detailing how the atlas enhances understanding of the DCIS microenvironment and the progression to invasive disease. DCIS refers to abnormal cells in breast milk ducts that have not yet invaded surrounding tissue, acting as a precursor to invasive ductal carcinoma. While mammograms and breast examinations have increased DCIS detection, many lesions do not progress, complicating treatment decisions.

Over the past three decades, routine mammography screening has led to overdiagnosis of DCIS, accounting for up to 25% of all breast cancer cases. Notably, genetic alterations in DCIS have been extensively studied, but knowledge about its tumor microenvironment remains limited. To generate a comprehensive cell atlas for DCIS, researchers employed single-cell and spatial profiling technologies, mapping over 850,000 cells from samples of normal tissue, DCIS, and invasive breast cancers.

They identified nine cell types and 60 cell states, revealing that changes in cancer cells and their microenvironment commence earlier than previously thought. The study also discovered "cancer stromal loops," ring-like structures composed of supportive tissue and vascular cells surrounding DCIS lesions, which foster tumor growth.

These findings suggest that remodeling of specific immune, stromal cell types, and myoepithelial cells in the DCIS tumor microenvironment (TME) contributes to cancer cell programing, facilitating DCIS progression. Further research is necessary to confirm these findings and explore their potential applications in diagnostics and prevention or treatment strategies.

Ultimately, the research could enable doctors to predict which patients require aggressive treatment and which may avoid it, aiding in personalized patient care.