Summary: Researchers have identified a distinct population of circulating tumor cells in the blood of breast cancer patients with brain metastases. This discovery is advancing efforts to develop a blood test that could identify patients at risk for brain metastasis and monitor disease progression and treatment response in real time.
Source: Houston Methodist.
Houston Methodist researchers move closer to a blood test that flags breast cancer patients at higher risk for brain metastasis and enables real-time monitoring of disease and treatment response.
A new proof-of-concept study has identified a distinct subgroup of circulating tumor cells (CTCs) found in the bloodstream of patients with breast cancer brain metastases (BCBM). The discovery, published online on August 4 in Nature Communications, sheds light on how some cancer “seeds” survive and later give rise to metastatic tumors in the brain, and it points toward more sensitive, non-invasive screening tools.
Lead author Dario Marchetti, Ph.D., director of the Biomarker Research Program at Houston Methodist Research Institute, explains that these circulating tumor cells are biologically different from other CTCs found in breast cancer patients. “Our study shows that CTCs associated with brain metastasis exhibit unique molecular features,” Marchetti said. “Understanding how these cells persist and eventually form metastases—sometimes years or decades after the primary tumor is treated—has been a major challenge in cancer research. This work brings us a step closer to developing blood-based tests that could detect metastatic disease earlier than imaging alone.”
Currently, magnetic resonance imaging (MRI) is the clinical standard for diagnosing brain metastasis. However, MRI typically detects lesions only after metastatic growth has reached a size that is often beyond the point where curative treatments are feasible. Clinical data indicate that roughly 20 percent of breast cancer patients will develop brain metastasis at some point, and brain metastatic disease is projected to become a leading cause of cancer mortality.
In this study, the research team performed an in-depth molecular analysis of CTCs isolated from the blood of patients with and without diagnosed brain metastases. First author Debasish Boral, Ph.D., reports that the team uncovered a 126-gene signature that is specific to CTCs linked to brain metastasis. By comparing whole-transcriptome profiles, the researchers identified signaling pathways and molecular features that distinguish these brain-tropic CTCs from other circulating tumor cells and from primary breast tumors.
The findings build on earlier work from Marchetti’s laboratory, which in 2015 reported four distinct CTC subsets implicated in cancer cell dormancy. Viable cancer cells can remain dormant in bone marrow or organs such as the brain, lungs and liver long after removal of a primary tumor. Dormant cells are difficult to detect with standard clinical tools, which complicates early treatment and reduces the chances of successful intervention.
Using the new gene-signature data, the Houston Methodist team is expanding their clinical study to include a larger, more diverse patient population. Their goal is to translate these molecular insights into two complementary liquid biopsy tools: (1) a screening assay capable of predicting the risk of brain micro-metastasis before lesions are visible on MRI, and (2) a real-time monitoring test to assess treatment efficacy in patients already diagnosed with brain metastases. Such liquid biopsies could help clinicians identify high-risk patients earlier, tailor interventions, and evaluate therapeutic response without invasive procedures.
The Nature Communications paper lists additional contributors from Houston Methodist Research Institute, Houston Methodist Hospital, The University of Texas MD Anderson Cancer Center, and the Cancer Science Institute of Singapore at the National University of Singapore. Collaborators include Monika Vishnoi, Haowen N. Liu, Wei Yin, Marc L. Sprouse, Jenny C. Chang, Antonio Scamardo, David S. Hong, Tuan Z. Tan, and Jean P. Thiery.
Research focus: The study, titled “Molecular characterization of breast cancer CTCs associated with brain metastasis,” reports that a distinct subset of CTCs is enriched in patients with brain metastases. The team identified a circulating tumor cell gene signature and associated signaling pathways that may drive the ability of these cells to establish brain metastases. These CTC biomarkers and pathways could serve as the basis for blood-based screening tests and for guiding treatment decisions and therapeutic monitoring in patients with BCBM.
Contact and source information: This summary is based on reporting from Houston Methodist. The original research article was published in Nature Communications on August 4, 2017 and is credited to the study authors led by Debasish Boral and Dario Marchetti.