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01.12.2017 | Research article | Ausgabe 1/2017 Open Access

BMC Cancer 1/2017

Tumor burden monitoring using cell-free tumor DNA could be limited by tumor heterogeneity in advanced breast cancer and should be evaluated together with radiographic imaging

Zeitschrift:
BMC Cancer > Ausgabe 1/2017
Autoren:
José Angel García-Saenz, Patricia Ayllón, Marion Laig, Daniel Acosta-Eyzaguirre, Marta García-Esquinas, Myriam Montes, Julián Sanz, Miguel Barquín, Fernando Moreno, Vanesa Garcia-Barberan, Eduardo Díaz-Rubio, Trinidad Caldes, Atocha Romero
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12885-017-3185-9) contains supplementary material, which is available to authorized users.
Jose Angel Garcia-Saenz, Fernando Moreno, Vanesa Garcia-Barberan, Eduardo Diaz-Rubio and Trinidad Caldes are members of CIBERONC network.

Abstract

Background

Accurate measurement of tumor burden in breast cancer disease is essential to improve the clinical management of patients. In this study, we evaluate whether the fluctuations in the fraction of PIK3CA mutant allele correlates with tumor response according to RECIST criteria and tumor markers quantification.

Methods

Eighty six plasma samples were analyzed by digital PCR using Rare Mutation Assays for E542K, E545K and H1047R. Mutant cfDNA and tumor markers CA15-3 and CEA were compared with radiographic imaging.

Results

The agreement between PIK3CA mutation status in FFPE samples and circulating tumor DNA (ctDNA) was moderate (K = 0.591; 95% IC = 0.371–0.811). Restricting the analysis to the metastatic patients, we found a good agreement between PIK3CA mutation status assessed in liquid and solid biopsy (K = 0.798 95%; IC = 0.586–1). ctDNA showed serial changes with fluctuations correlating with tumor markers 15.3 and CEA in 7 out of 8 cases with Pearson correlation coefficients ranging from 0.99 to 0.46 and from 0.99 to 0.38 respectively. Similarly, fluctuations in the fraction of PIK3CA mutant allele always correlated with changes in lesion size seen on images, although in two cases it did not correlate with treatment responses as defined by RECIST criteria.

Conclusion

oncogenic mutation quantification in plasma samples can be useful to monitor treatment outcome. However, it might be limited by tumor heterogeneity in advanced disease and it should be evaluated together with radiographic imaging.
Zusatzmaterial
Additional file 1: Clinical and pathological variables. (XLSX 16 kb)
12885_2017_3185_MOESM1_ESM.xlsx
Additional file 2: Limit of detection and limit of quantification estimation according to ICH guidelines. (XLSX 30 kb)
12885_2017_3185_MOESM2_ESM.xlsx
Additional file 3: Performance of PIK3CA assays on cfDNA. Data from sample chips are displayed in a scatter plot based on color of FAM and VIC events. Plots A, C and E correspond to a negative samples. Plots B, D and F correspond to positive samples for the H1047R, E545K and E542K mutation respectively. The mutation is labeled with FAM (blue data points) whereas wild-type is labeled with VIC (red data points). Yellow cluster represent the no amplification cluster. (PPTX 153 kb)
12885_2017_3185_MOESM3_ESM.pptx
Additional file 4: Serial plasma PIK3CA mutation levels and treatment outcome, assessed according to RECIST criteria v.1.1. SD = stable disease, PR = partial response, PD = progressive disease of individual cases. (PPTX 78 kb)
12885_2017_3185_MOESM4_ESM.pptx
Literatur
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