The promise of ctDNA-based, molecularly-driven early switch therapy from PADA-1 to SERENA-6
Leandro Jonata Carvalho Oliveira1,2,3, Max Senna Mano4,5, Carlos Barrios4,6,7
1Grupo Brasileiro de Estudos em Câncer de Mama (GBECAM), Porto Alegre, RS, Brazil. leandrojco1986@gmail.com.
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.
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