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01-10-2019 | Metastasis | 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

Authors: 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

Published in: Breast Cancer Research and Treatment | Issue 3/2019

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.

Trial registration

NCT01612871, registered on June 6th, 2012; https://clinicaltrials.gov/ct2/show/NCT01612871.

Available only for authorised users

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Title: PIK3CA mutations early persistence in cell-free tumor DNA as a negative prognostic factor in metastatic breast cancer patients treated with hormonal therapy
Authors: 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
Publication date: 01-10-2019
Publisher: Springer US
Keywords: Metastasis
Breast Cancer
Breast Cancer
Biomarkers
Published in: Breast Cancer Research and Treatment / Issue 3/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05349-y

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