Liquid Biopsy Biomarkers Distinguish Inflammatory Breast Cancer and Support Monitoring

Inflammatory breast cancer is among the most aggressive forms of breast malignancy and remains challenging to diagnose and monitor. Obtaining tumor tissue can be difficult, and standard genome and RNA sequencing often fail to distinguish it from other subtypes. A less invasive, blood-based approach could improve detection and longitudinal assessment. Addressing this need, researchers have identified circulating genomic biomarkers that differentiate inflammatory breast cancer from non-inflammatory breast cancer using an enhanced RNA sequencing method.

The University of Texas MD Anderson Cancer Center (Houston, TX, USA), in collaboration with The University of Texas at Austin (Austin, TX, USA) and the University of Hawai'i Cancer Center (Honolulu, HI, USA), identified blood-based genomic signatures characteristic of inflammatory breast cancer (IBC). The work centers on TGIRT sequencing, described as an improved method that captures a comprehensive range of RNA species in clinical samples. The findings are published in Science Advances.

Image: Researchers identified blood-based genomic signatures characteristic of inflammatory breast cancer (photo courtesy of Shutterstock)

TGIRT sequencing uses a specialized, robust enzyme capable of functioning in extreme conditions, enabling reliable capture of complex and fragmented RNAs that standard RNA-sequencing enzymes often miss. Leveraging this approach, the team developed methods to analyze protein-coding genes specific to IBC tumors. The technique supported parallel interrogation of tumors, peripheral blood cells, and plasma to discover circulating biomarkers.

Using TGIRT sequencing, investigators observed that blood from patients with IBC contained high levels of noncoding RNAs and increased white blood cell counts relative to samples from healthy or non-IBC individuals. In plasma from IBC cases, intron RNA fragments—the noncoding sequences normally removed during splicing—were overrepresented, whereas healthy blood predominantly contained degraded messenger RNA fragments. Together, these patterns distinguished IBC from other breast cancer subtypes across sample types. The authors state that these biomarkers provide a less invasive path for early diagnosis, disease progression monitoring, and development of treatment strategies tailored to this aggressive subtype.

“These findings provide new insights into inflammatory breast cancer that should enable clinicians to monitor disease progression simply through liquid biopsy. Because it is so difficult to obtain tumor samples, these blood-based biomarkers could be truly transformative in developing treatments for this patient population,” said Savitri Krishnamurthy, M.D., professor of Anatomic Pathology at The University of Texas MD Anderson Cancer Center.

Related Links
UT MD Anderson Cancer Center
The University of Texas at Austin
University of Hawai'i Cancer Center