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Breast Cancer Research and Treatment

, Volume 177, Issue 3, pp 659–667 | Cite as

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

  • William JacotEmail author
  • 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
Clinical trial
  • 237 Downloads

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.

Keywords

Breast cancer PIK3CA Cell-free DNA Prognostic biomarker 

Abbreviations

BC

Breast cancer

cfDNA

Cell-free DNA

CDK

Cyclin-dependent kinase

ER+

Estrogen-receptor-positive

HT

Hormonal therapy

mBC

Metastatic breast cancer

mTOR

Mammalian target of rapamycin

PI3K

Phosphatidylinositol 3-kinase

PI3KCA

PI3K catalytic subunit alpha

PFS

Progression-free survival

RB

Retinoblastoma

95% CI

95% confidence interval

Notes

Acknowledgements

The authors want to thank Dr. Hélène de Forges for her substantive writing and editing assistance.

Author contributions

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.

Funding

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.

Ethical approval

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.

Supplementary material

10549_2019_5349_MOESM1_ESM.docx (32 kb)
Supplementary material 1 (DOCX 31 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • William Jacot
    • 1
    • 3
    • 4
    Email author
  • Florence Dalenc
    • 2
  • Evelyne Lopez-Crapez
    • 3
    • 4
  • Leonor Chaltiel
    • 5
  • Anna Durigova
    • 1
  • Nathalie Gros
    • 3
  • Nicolas Lozano
    • 6
  • Jean-Louis Lacaze
    • 2
  • Stéphane Pouderoux
    • 1
  • Laurence Gladieff
    • 2
  • Gilles Romieu
    • 1
  • Henri Roché
    • 2
  • Thomas Filleron
    • 5
  • Pierre-Jean Lamy
    • 6
  1. 1.Department of Medical Oncology, Institut du Cancer de Montpellier (ICM)Univ. MontpellierMontpellier Cedex 5France
  2. 2.Department of Medical OncologyInstitut Claudius Regaud, IUCT-OToulouseFrance
  3. 3.Translational Research Unit, Institut du Cancer de Montpellier (ICM)Univ. MontpellierMontpellierFrance
  4. 4.INSERM, U1194MontpellierFrance
  5. 5.Department of BiostatisticsInstitut Claudius Regaud, IUCT-OToulouseFrance
  6. 6.Institut d’Analyse Génomique, Imagenome-InovieClinique BeauSoleilMontpellierFrance

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