Abstract
The presence of circulating tumor cells (CTCs), detected as a form of liquid biopsy is associated with poor survival in both early and metastatic breast cancer. Monitoring tumor biology based on intrinsic subtypes delivers treatment-relevant information on the heterogeneity or biomarker conversion between primary and metastatic tumors. This study aimed to correlate the change of the apoptotic and intact CTC counts with mRNA-assessed intrinsic subtype change. Thirty-four breast cancer patients with available triplets of primary tumors, distant metastasis biopsies and data on intact and apoptotic CTC dynamics were included in the analysis. The intrinsic subtype was determined per RT-qPCR quantification of the gene expression ESR1, PGR, ERBB2 and MKI67. Both luminal (p = 0.038) and triple negative (p = 0.035) patients showed a significant downregulation of apoptotic CTCs. Repeated biopsies of distant metastatic sites, as well as determining a potential shift of the intrinsic subtype, combined with data on intact and apoptotic CTC dynamics from liquid biopsies might help personalize systemic therapy and generate additional surrogate markers for successful systemic therapy.
Highlights
Performing a liquid biopsy by repeatedly measuring the rates of circulating tumor cells (CTCs) or circulating tumor DNA rates in serum is a non-invasive method of monitoring diseaseCancers 2019, 11, 342; doi:10.3390/cancers11030342 www.mdpi.com/journal/cancersCancers 2019, 11, 342 activity in all phases of breast cancer [1,2,3,4]
We have previously reported intrinsic subtype-related and site-related discrepancies in tumor biology between primary and metastatic tumors by mRNA-assessment, possibly based on tumor heterogeneity or biomarker conversion, underlining the importance of re-biopsies and biopsies of distant metastases
The presence of at least five CTCs in 7.5 mL of blood is associated with reduced progress-free survival (PFS) and overall survival (OS) in patients with metastatic breast cancer (MBC) [11]
Summary
Performing a liquid biopsy by repeatedly measuring the rates of circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) rates in serum is a non-invasive method of monitoring diseaseCancers 2019, 11, 342; doi:10.3390/cancers11030342 www.mdpi.com/journal/cancersCancers 2019, 11, 342 activity in all phases of breast cancer [1,2,3,4]. Performing a liquid biopsy by repeatedly measuring the rates of circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) rates in serum is a non-invasive method of monitoring disease. Determining the tumor biology, preferably based on the intrinsic subtype, delivers additional information on tumor heterogeneity or tumor marker conversion between primary (PT) and metastatic tumors (MT) [7,8]. We have previously reported intrinsic subtype-related and site-related discrepancies in tumor biology between primary and metastatic tumors by mRNA-assessment, possibly based on tumor heterogeneity or biomarker conversion, underlining the importance of re-biopsies and biopsies of distant metastases. Alternative methods for following disease activity and analyzing tumor biomarker dynamics, including liquid biopsies, were devised. Aside from the possibility of tumor biology monitoring per se, the detection of CTCs has a prognostic value [10]. Several studies have demonstrated the usefulness of serial CTC enumeration as a means of monitoring the efficacy of therapy [12]
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