Erschienen in:
11.07.2019 | Clinical trial
PIK3CA mutations early persistence in cell-free tumor DNA as a negative prognostic factor in metastatic breast cancer patients treated with hormonal therapy
verfasst von:
William Jacot, Florence Dalenc, Evelyne Lopez-Crapez, Leonor Chaltiel, Anna Durigova, Nathalie Gros, Nicolas Lozano, Jean-Louis Lacaze, Stéphane Pouderoux, Laurence Gladieff, Gilles Romieu, Henri Roché, Thomas Filleron, Pierre-Jean Lamy
Erschienen in:
Breast Cancer Research and Treatment
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Ausgabe 3/2019
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Abstract
Purpose
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.
Methods
Between June 2012 and January 2014, 39 patients were prospectively included in a dedicated clinical trial (NCT01612871). Blood sampling was performed before (M0) and 4 weeks (M1), 3 months (M3) and 6 months (M6) after HT initiation, and at tumor progression. Patients were followed until progression or until the end of the study (2 years). Mutation detection was performed using droplet-based digital PCR (ddPCR). Progression-free survival (PFS) was used as primary endpoint.
Results
Median age at inclusion was 63 years (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 1 year: 40% versus 76.7%; p = 0.0053).
Conclusions
Four-week persistence of cfDNA PIK3CA mutation appears highly correlated with PFS.