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

BMC Cancer

Research Article

Daniel Acosta-Eyzaguirre¹  Fernando Moreno²  Patricia Ayllón²  Eduardo Díaz-Rubio²  Vanesa Garcia-Barberan²  Trinidad Caldes²  José Angel García-Saenz²  Atocha Romero³  Miguel Barquín⁴  Julián Sanz⁵  Myriam Montes⁶  Marta García-Esquinas⁷  Marion Laig⁸ 

[1] Medical Oncology Department, Centro Integral Oncológico Clara Campal HM hospitals, Madrid, Spain;Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain;Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain;Medical Oncology Department, Hospital Universitario Puerta de Hierro Madrid, 28222, Majadahonda, Madrid, Spain;Medical Oncology Department, Hospital Universitario Puerta de Hierro Madrid, 28222, Majadahonda, Madrid, Spain;Pathology Department, Hospital Clínico San Carlos, Madrid, Spain;Radiology Department, Hospital Clínico San Carlos, Madrid, Spain;Radiology Department, Hospital Clínico San Carlos, Madrid, Spain;Nuclear Medicine Department, Hospital Clínico San Carlos, Madrid, Spain;Thermo Fisher Scientific, Waltham, Massachusetts, USA;

关键词: Breast cancer;    dPCR;    PIK3CA;    cfDNA;   

DOI  :  10.1186/s12885-017-3185-9

 received in 2016-08-31, accepted in 2017-03-09,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAccurate 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.MethodsEighty 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.ResultsThe 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.Conclusiononcogenic 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.

【 授权许可】

CC BY   
© The Author(s). 2017