Nevertheless the frequency of CTCs

Nevertheless, the frequency of CTCs was higher in patients with metastatic breast cancer, which is to be expected because cancer LY3009120 from the original clone that caused the metastasis probably had features favoring their spread throughout the body. When we take HER2+ CTC counts ≥ 3 as a “strong” HER2 status, significant differences could be found between specimens positive or negative for HER2, providing a possible marker for metastasis. Of the 71 patients, only 12 had not received any treatment for breast cancer before the study, and the other 59 had been treated with a variety of treatments but no targeted therapy. There was no significant difference in the CTC counts between patients with or without past treatments and this was probably owing to the patients’ past treatment not effectively controlling tumor growth. This may also lead to a similar HER2+ CTC count between the 2 groups of patients. Subsequent studies should explore the difference in HER2+ CTC count according to a history of HER2-targeted therapy. Among the 71 patients with breast cancer, 31 (43.7%) had an HER2+ tumor. Among the HER2+ patients, 41.9% (13/31) were found to be HER2+ based on CTC ≥ 1, and 25.8% (8/31) were positive based on CTC ≥ 3. This is in agreement with previous studies performed using the CellSearch platform, which showed that 30% to 40% of patients with HER2+ tumor at pathologic examination also had HER2+ CTCs.14, 27 Among HER2− patients by pathologic examination, 1 (2.5%) patient was found to have ≥ 3 HER2+ CTCs. This frequency is lower than in a previous study that showed that 20% of patients with HER2− tumor by pathologic examination had HER2+ CTCs. This discrepancy might be owing to a variety of reasons, including the sample size, the number of sections examined by the pathologists, and cancer treatment history. Moreover, in the present study, 14 (35.0%) HER2− patients by pathologic examination had 1 or 2 HER2+ CTCs. Although there is not enough evidence to explain the meaning of small numbers of CTCs in cancer treatments, it is worth studying the clinical value of those low counts in a future study. Taken together, these results highlight that pathologic examination might miss some foci of more aggressive disease and that irrespective of the tumor’s characteristics, the CTCs are responsible for the metastatic spread, and their characteristics should be taken first into account for patient management. This also highlights the heterogeneous nature of tumors. Indeed, a tumor may arise from different clones leading to tumor areas with different biological characteristics and aggressiveness. In addition, HER2− breast cancer cells may spontaneously transform into HER2+ CTCs. The cells responsible for metastatic spread and disease progression should be regarded as the most dangerous ones, and the treatments should be based on those cells. Nevertheless, in the pre-trastuzumab era, it has been shown that HER2+ CTCs in patients with stage I to III breast cancer were associated with a poor prognosis. On the other hand, another study showed that discrepancies in HER2 and estrogen receptor statuses between the primary tumor and CTCs had no impact on the prognosis of metastatic breast cancer. Clinical studies are still necessary to prove this point. The present study is not without limitations. Indeed, the study population was small and heterogeneous, preventing any immediate clinical application of the results. In addition, no comparison was made with other methods for detecting CTCs, such as the CellSearch system. The present study was a proof-of-concept study for the use of the LiquidBiopsy system for the detection of HER2+ CTCs in patients with breast cancer. At this step, our results cannot be used to determine clinically relevant cutoff points. Additional studies are necessary to determine the prognostic significance of CTCs detected using the LiquidBiopsy system. Nevertheless, the present study indicates that the LiquidBiopsy system can be used to determine molecular characteristics of CTCs. Future studies could examine other characteristics of breast cancer cells such as estrogen receptors, progesterone receptor, and Ki67. This feature of the LiquidBiopsy system could outperform the CellSearch system for individualized medicine because the CellSearch system counts CTCs based on the CK+ CD45- phenotype.