A groundbreaking study suggests that a simple blood test could help predict how patients with advanced breast cancer respond to targeted therapies, potentially transforming treatment strategies for metastatic disease.
According to the World Health Organization, roughly 2.3 million women worldwide were diagnosed with breast cancer in 2022. While treatments such as surgery, chemotherapy, radiation, immunotherapy, and targeted therapies exist, success rates vary widely depending on cancer type, stage, and individual patient health, making it challenging for doctors to forecast treatment effectiveness.
Now, researchers have identified a promising tool: a liquid biopsy that measures circulating tumor DNA (ctDNA) in the bloodstream to monitor treatment response in real-time. The study, published in Clinical Cancer Research, analyzed blood samples from 167 participants in the plasmaMATCH trial, all of whom had advanced breast cancer.
Tracking ctDNA for Treatment Response
ctDNA consists of tiny fragments of DNA shed by tumors into the blood. Researchers grouped participants by cancer type and genetic mutations, such as ESR1, HER2, AKT1, AKT, or PTEN, as well as a group with triple-negative breast cancer lacking targetable mutations. Blood samples were taken before treatment and four weeks after therapy began to measure ctDNA levels.
Findings showed a clear link between ctDNA levels and treatment outcomes:
In the first group, participants with undetectable ctDNA after four weeks experienced 10.6 months of progression-free survival, compared with 3.5 months for those with detectable ctDNA. Nearly half (46.2%) of patients with low ctDNA levels responded to treatment, versus just 7.9% for those with high levels.
In the second group, low pre-treatment ctDNA predicted 10.2 months of progression-free survival, compared to 4.4 months for higher ctDNA levels. Participants whose ctDNA became undetectable had 12 months of cancer-free progression and an 85.7% response rate, compared to 4.3 months and 11.4% among those with detectable ctDNA.
“Patients with low or undetectable ctDNA consistently had better outcomes, including longer progression-free survival and higher response rates,” said Iseult Browne, MD, clinical research fellow at The Institute of Cancer Research, London, and first author of the study. “These findings support ctDNA as a non-invasive biomarker for predicting outcomes and monitoring treatment response.”
Implications for Metastatic Breast Cancer
Experts not involved in the study emphasize its potential impact on metastatic breast cancer care, where tumors have spread to organs such as the liver, lungs, or bones.
“Detecting and monitoring metastatic disease is more challenging, and ctDNA testing provides a precise way to track treatment response,” said Richard Reitherman, MD, PhD, medical director of breast imaging at MemorialCare Breast Center in Fountain Valley, CA. “This approach can identify responders and non-responders earlier, allowing treatment adjustments that could improve patient outcomes.”
Richard Zelkowitz, MD, medical director of breast oncology at Hartford HealthCare Cancer Institute, called the results “extremely exciting” for patients with hormone-sensitive advanced breast cancer. “Being able to predict treatment effectiveness through a simple blood test is a game-changer, offering more personalized care and potentially better survival and quality of life for patients,” he said.
While further research is needed to directly link ctDNA monitoring to long-term survival benefits, these findings highlight a promising step toward more precise, individualized treatment for patients battling advanced breast cancer.
