The promise of ctDNA-based, molecularly-driven early switch therapy from PADA-1 to SERENA-6.

PURPOSE: Circulating tumor DNA (ctDNA) enables early detection of ESR1 mutations in hormone receptor-positive, HER2-negative metastatic breast cancer. Building on the PADA-1, the SERENA-6 trial demonstrated significant progression-free survival and quality-of-life benefits from ctDNA-guided early endocrine switching before radiologic progression.

METHODS

We examine the evolving clinical utility of liquid biopsy in this setting and review evidence from trials evaluating biomarker-guided treatment adaptation. We also compare imaging- versus biomarker-guided strategies.

CONCLUSION

This review outlines the key challenges to validating and implementing ctDNA-guided early endocrine switching in routine clinical practice and discusses its potential to reshape monitoring and decision-making in metastatic hormone receptor-positive, HER2-negative breast cancer.