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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.

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.
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García-Saenz JA, Ayllón P, Laig M, Acosta-Eyzaguirre D, García-Esquinas M, Montes M, Sanz J, Barquín M, Moreno F, Garcia-Barberan V, Díaz-Rubio E, Caldes T, Romero A,


García-Saenz JA, Ayllón P, Laig M, Acosta-Eyzaguirre D, García-Esquinas M, Montes M, Sanz J, Barquín M, Moreno F, Garcia-Barberan V, Díaz-Rubio E, Caldes T, Romero A, (click to view)

García-Saenz JA, Ayllón P, Laig M, Acosta-Eyzaguirre D, García-Esquinas M, Montes M, Sanz J, Barquín M, Moreno F, Garcia-Barberan V, Díaz-Rubio E, Caldes T, Romero A,

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BMC cancer 2017 03 2217(1) 210 doi 10.1186/s12885-017-3185-9
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.

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