Gene expression signatures in circulating tumor cells correlate with response

© Journal of Laboratory and Precision Medicine. All rights reserved. J Lab Precis Med 2018;3:33 jlpm.amegroups. com Breast cancer is the most common cancer among women worldwide (1). Despite the development of new therapeutic strategies, metastatic breast cancer (MBC) remains an incurable disease characterized by a high clinical variability, partly linked to the molecular heterogeneity of both the primary tumor and its metastases (2). This heterogeneity can be the result of the intrinsic cancer-related genomic instability and/or be induced by therapies (3). The biological discordance between primary tumor and metastases is usually paralleled by changes in the genomic/transcriptional landscape of the different tumor sites determining resistance to ongoing therapies and/or acquired sensitivity to new therapies. For this reason, circulating tumor cells (CTC) are considered a special window to study the evolution of the metastatic disease, allowing, in primis, the possibility to monitor the tumor load in the peripheral blood (4,5). Indeed, it has been definitely demonstrated the prognostic (overall survival and progression free survival) and predictive value of both the absolute number of circulating tumor cells before the beginning of a new therapeutic line as well as the change in CTC number upon therapy (6-8). However, the clinical utility of CTC, i.e., their ability to improve the patient outcome by guiding therapy, remains to be demonstrated and, after the disappointing results of the SWOG500 trial (9), it is now under investigation in numerous prospective, randomized, multicenter clinical trials (e.g., STIC CTC METABREAST, DETECT V, and COMETI P2) (5). In the meantime, scientists are exploring the advantage of going beyond the simple CTC enumeration by characterizing CTC from a molecular point of view. The purpose is to use CTC as a surrogate for the conventional tissue biopsy, to non-invasively evaluate the cancer genomic/transcriptomic/proteomic landscape and its evolution during treatment, in order to early detect drugresistance and, possibly, predict new therapeutic targets (5). The paper of Bredemeier et al. fits into these lines of research and aims to correlate the gene expression profile of CTC with the response to therapy (10). Specifically, it evaluates the expression of 46 genes in CTC samples, enriched by Adna test, of 45 patients affected by MBC, enrolled before starting of a new therapeutic line, at the time of disease progression (PD). CTC were assessed at three time points: before the beginning of the new therapy (T0), and at two subsequent follow-ups (T1 and T2), about 8–12 weeks from each other. At the first follow-up (T1), patients were divided into responders (R) and non-responders (NR) depending on the presence of disease progression, as assessed by RECIST criteria. At T2 patients were classified as overall responder (OR) and overall non-responder (ONR) if the progression status were unchanged with respect to T1. Late responders and late non-responders, that is NR patients at T1 evaluated as responders in T2 and R patients at T1 undergoing progression in T2, were not further assessed in the study. Editorial