PIK3CA mutations early persistence in cell-free tumor DNA as a negative prognostic factor in metastatic breast cancer patients treated with hormonal therapy

Abstract

The identification of biomarkers of hormonal therapy (HT) failure would allow tailored monitoring in metastatic breast cancer (mBC) patients. PIK3CA gene mutation is one of the most frequent events in mBC and is associated with HT resistance. We evaluated the early prognostic value of cell-free DNA (cfDNA) PIK3CA detection in first-line HT-treated mBC patients. Between June 2012 and January 2014, 39 patients were prospectively included in a dedicated clinical trial (NCT01612871). Blood sampling was performed before (M0) and 4weeks (M1), 3months (M3) and 6months (M6) after HT initiation, and at tumor progression. Patients were followed until progression or until the end of the study (2years). Mutation detection was performed using droplet-based digital PCR (ddPCR). Progression-free survival (PFS) was used as primary endpoint. Median age at inclusion was 63years (range 40-86). Most patients (34/39) received an aromatase inhibitor and presented a non-measurable disease (71.8%). PIK3CA mutations were reported in 10 (27.8%) and 5 (14.3%) cases at M0 and M1, respectively. The persistence of a detectable circulating mutation at M1 was highly correlated with a worse progression-free survival (PFS), rate at 1year: 40% versus 76.7%; p = 0.0053). Four-week persistence of cfDNA PIK3CA mutation appears highly correlated with PFS. NCT01612871, registered on June 6th, 2012; https://clinicaltrials.gov/ct2/show/NCT01612871 .