When visualized as a traditional map, the new breast cancer atlas resembles an archipelago, where distinct breast cancer subtypes that share common molecular features, treatment responses and clinical outcomes populate different “islands.” Credit: Brian Lehmann
A new molecular map of breast cancer has identified novel forms of the disease and provides a foundation for selecting personalized treatments guided by a tumor’s molecular characteristics rather than standard pathology alone.
One of the long-standing challenges in cancer genomics has been the difficulty of comparing datasets generated across different studies, sequencing platforms and analytical methods. To overcome these barriers, the researchers adapted computational approaches originally developed for single-cell genomics, enabling the integration of thousands of breast cancer transcriptomes into a unified analytical framework.
The resulting atlas groups breast cancers into interconnected clusters that share common molecular features, treatment responses and clinical outcomes. When visualized as a map, the atlas resembles an archipelago, with biologically related tumor populations occupying distinct “islands” within a broader molecular landscape.
According to the study results, the atlas reveals substantial biological diversity within traditional breast cancer categories, demonstrating that current classifications do not fully capture clinically relevant differences among tumors. The atlas defines a biologically distinct aggressive basal-luminal progenitor subtype of triple-negative breast cancer with potential vulnerabilities to RTK/MAPK-targeted and anti-angiogenic therapies.
The atlas also identifies subsets of HER2-positive tumors that are most dependent on HER2 signaling and could benefit from specific types of HER2 kinase inhibitors. The study uncovers a hidden neuroendocrine form of breast cancer associated with worse outcomes following standard chemo-endocrine therapy and points to FGFR1 as a potential therapeutic target.
Researchers envision that a patient’s tumor could eventually be positioned on this atlas to identify the most appropriate therapies and improve treatment selection for clinical trials.
In addition to developing the atlas, the researchers also created a tool that can assign tumors to subtypes using standard bulk RNA sequencing data to guide future research studies and clinical trials.
“The next critical step is prospective testing to determine whether treatment decisions guided by these transcriptional subtypes improve patient outcomes,” said corresponding author Brian Lehmann, research associate professor of medicine at Vanderbilt Health. “Our goal is to match patients to therapies based on the biology of their tumors. This atlas provides both a road map and a practical framework for achieving that vision.”
Data from Vanderbilt University Medical Center