PIK3CA mutations early persistence in cell-free tumor DNA as a negative prognostic factor in metastatic breast cancer patients treated with hormonal therapy
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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 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.
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).
Four-week persistence of cfDNA PIK3CA mutation appears highly correlated with PFS.
NCT01612871, registered on June 6th, 2012; https://clinicaltrials.gov/ct2/show/NCT01612871.
KeywordsBreast cancer PIK3CA Cell-free DNA Prognostic biomarker
Metastatic breast cancer
Mammalian target of rapamycin
PI3K catalytic subunit alpha
- 95% CI
95% confidence interval
The authors want to thank Dr. Hélène de Forges for her substantive writing and editing assistance.
Study concept/design/funding: WJ, P-JL, EL-C, FD, and AD. Reagents/materials/analysis tools contribution: NG, P-JL, NL, and EL-C. Patients’ inclusion and follow-up: WJ, FD, AD, J-LL, SP, LG, GR, and HR. Acquisition of data: NG, WJ, P-JL, and EL-C. Statistical analysis: LC and TF. Analysis and interpretation of data: WJ, P-JL, and EL-C. Drafting of the manuscript: NG, WJ, P-JL, EL-C, FD, LC, and TF. All the authors participated to the critical revision and validation of the final manuscript.
This ancillary study was supported by the “Fond pour la Recherche Val d’Aurelle” grant. This research was supported by the SIRIC Montpellier Cancer Grant INCa_Inserm_DGOS_12553.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
This study was approved by the CPP (Ethics Committee) Sud-Ouest et Outre-Mer III and registered under the reference No. 2012/25. This study was performed in accordance with the Declaration of Helsinki.
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