Studies have suggested that circulating tumor DNA (ctDNA) analysis may provide an assessment of the genomic profile of advanced cancer without the need for repeating tumor biopsy. This study aims to investigate the accuracy of ctDNA testing and its ability to select patients for mutation-directed therapy among patients with advanced breast cancer.

This multicohort, open-label, phase 2a, platform trial included a total of 1,051 patients with advanced breast cancer. The patients were randomized into four parallel cohorts: cohort A included patients with ESR1 mutations (treated with extra-dose fulvestrant), cohort B included patients with HER2 mutations (neratinib or standard-dose fulvestrant), cohort C included patients with AKT1 mutations estrogen-positive (capivasertib plus fulvestrant), and cohort D included patients with AKT1 mutations estrogen-negative (capivasertib). The primary objective of the study was the objective response rate.

Of 1,051 patients registered, the response was available for 1,034 patients. At a combined median follow-up of 14.4 months, cohorts B (25%) and C (22%) exceeded the number of target responses. Cohorts A (8%) and D (11%) did not reach the target responses.

The research concluded that ctDNA testing offered accurate genotyping that enabled the selection of mutation-directed therapies in breast cancer patients, with the effects being more significant against HER2 and AKT1 mutations.