Circulating tumor DNA (ctDNA) analysis is emerging as a valuable tool for guiding treatment decisions in both advanced and early-stage breast cancer, potentially revolutionizing how the disease is managed. Two recent studies highlight the clinical implications of ctDNA testing, offering new insights into personalized treatment approaches and long-term outcome prediction.
ctDNA Analysis in Advanced Breast Cancer
A study published in Precision Clinical Medicine by researchers from the PRAEGNANT Network in Germany explored the clinical implications of ctDNA testing in advanced or metastatic breast cancer. The study, which analyzed 49 patients using the FDA-approved Guardant360 CDx test, revealed that 76% of patients had at least one somatic mutation. The most frequently altered genes were TP53 (29%), PIK3CA (24%), FGFR1 (20%), and ATM (16%). Mutations in BRCA1 and BRCA2 were found in 6% and 8% of patients, respectively, while 12% of patients exhibited ESR1 mutations.
These findings underscore the potential of ctDNA as a valuable biomarker, especially for patients with hormone receptor-positive, HER2-negative breast cancer. The study also revealed that ctDNA testing influenced treatment decisions in 35% of cases, enabling eligibility for therapies like alpelisib, elacestrant, and capivasertib.
"Our research shows that ctDNA analysis offers a deeper understanding of the genetic makeup of advanced breast cancer, providing essential insights that enable more personalized treatment approaches," said Dr. Peter A. Fasching, corresponding author of the study. "This non-invasive method has the potential to transform how metastatic breast cancer is managed and treated."
ctDNA in Early-Stage Breast Cancer
Data from the investigational phase 2 PELOPS trial (NCT02764541), presented at the 2024 San Antonio Breast Cancer Symposium, support the role of ctDNA in predicting outcomes in HR-positive early breast cancer. The study found that the presence of ctDNA at baseline was correlated with larger pathological tumor size and endocrine therapy sensitivity.
The PELOPS trial included 49 patients with stages I-III HR-positive, HER2-negative breast cancer who were randomized to receive either neoadjuvant endocrine therapy plus palbociclib (Ibrance) or neoadjuvant endocrine therapy alone. Plasma samples were collected at baseline and presurgery. Baseline ctDNA detection was higher in patients with higher residual cancer burden (RCB) scores (P = 0.005). Higher tumor fraction was associated with pathological stage at surgery (P = 0.0006), and higher RCB scores after neoadjuvant endocrine therapy were also associated with pathological stage at surgery (P = 0.0014).
"Our findings suggest that ctDNA has the potential to provide valuable insights into tumor burden, sensitivity to endocrine therapy and the emergence of endocrine resistance mutations," Albert Grinshpun, MD, MSc, and colleagues wrote in their poster.
Implications for Clinical Practice
The integration of ctDNA testing into everyday clinical practice could revolutionize breast cancer treatment, offering a more precise and tailored approach. By identifying specific genetic mutations, clinicians can personalize therapies, improving outcomes and potentially reducing resistance. These studies highlight the importance of adopting ctDNA testing more widely and emphasize the need for further research to maximize its potential in revolutionizing cancer care. However, Grinshpun and colleagues noted that the PELOPS trial results are limited by the sample size but merit further investigation of the role of ctDNA as a tool to predict sensitivity to endocrine therapy and long-term outcomes.
