Personalized ctDNA detection and genomic profiling in the NeoRHEA Study.

Area of Science:

• Oncology
• Molecular Diagnostics
• Genomics

Background:

• Circulating tumor DNA (ctDNA) is an emerging biomarker for early hormone receptor-positive (HR+), HER2-negative breast cancer.
• The NeoRHEA trial investigated neoadjuvant palbociclib plus endocrine therapy in this patient population.

Purpose of the Study:

• To assess the utility of ctDNA as a biomarker in early HR+/HER2- breast cancer treated with neoadjuvant therapy.
• To correlate ctDNA dynamics and genomic alterations with treatment response.

Main Methods:

• The RaDaR assay was used to detect ctDNA in plasma samples from the NeoRHEA trial.
• Samples were collected at multiple time points: pre-treatment, post-cycle 1, pre-surgery, and 1 month post-surgery.
• Genomic alterations (MYC, PIK3CA, FAT1) were analyzed.

Main Results:

• Baseline ctDNA was detected in 55% of patients, decreasing significantly during treatment and becoming undetectable post-surgery.
• Higher baseline ctDNA was associated with grade 3 tumors and higher residual cancer burden (RCB) 3.
• Specific genomic alterations (MYC, PIK3CA, FAT1) were enriched in different response groups.

Conclusions:

• Baseline ctDNA detection is a significant predictor of poor response to neoadjuvant palbociclib plus endocrine therapy in HR+/HER2- breast cancer.
• ctDNA serves as a valuable biomarker for guiding treatment decisions in this breast cancer subtype.
• Further research into ctDNA dynamics and genomic profiling can refine treatment strategies.