Clinical significance of circulating tumor cells (CTCs) with respect to optimal cut-off value and tumor markers in advanced/metastatic breast cancer

Shiomi-Mouri, Yukako; Kousaka, Junko; Ando, Takao; Tetsuka, Rie; Nakano, Satoshi; Miwa, Yosuke; Fujii, Kenichi; Akizuki, Miwa; Imai, Tsuneo; Fukutomi, Takashi; Kobayashi, Katsumasa

doi:10.1007/s12282-014-0539-x

Cited by 25 publications

(20 citation statements)

References 21 publications

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“…13,14 Second, there is no consensus about the cutoff value for diagnosis and prognosis. [15][16][17] Finally, most studies are based on the CellSearch platform because it is the only United States Food and Drug Administrationapproved platform currently, but the CellSearch platform has been shown to have a number of limitations. Indeed, the CellSearch platform is based on the restricted phenotypic definition of a CTCs (cells of epithelial origin expressing cytokeratin but not CD45) and so excludes many classes of informative cells because the system only allows for the detection of CK þ CD45 À cells and does not allow customization for the detection of other cellular characteristics, such as the expression of HER2, estrogen receptor, and progesterone receptor.…”

Section: Introductionmentioning

confidence: 99%

Detection of HER2-positive Circulating Tumor Cells Using the LiquidBiopsy System in Breast Cancer

Chen

Zhang

Huang

et al. 2019

Clinical Breast Cancer

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This study aimed to use the LiquidBiopsy system and immunofluorescence to measure human epidermal growth factor receptor 2 in circulating breast cancer cells. Seventy-one patients with breast cancer and 107 control provided blood samples. The results indicated that the LiquidBiopsy system may be useful for detecting human epidermal growth factor receptor 2 expression levels on CTC as it was positively correlated with pathologic examination. Background: Most previous studies of circulating tumor cells (CTCs) are based on the CellSearch platform, but CellSearch has a number of limitations. This study aimed to use the LiquidBiopsy system and immunofluorescence to test the human epidermal growth factor receptor 2 (HER2) status of CTCs in patients with breast cancer. Materials and Methods: The LiquidBiopsy system was used to detect HER2-positive (HER2 þ) cells in whole blood by microfluidic immunomagnetic bead screening and immunofluorescence assay, according to the manufacturer;s instructions. HER2 expression on CTCs was assessed using the Ariol system, calibrated through spiking experiments of 100 cells (BT474, SKBR3, A431, and MDA-MB-231) and 2.5 Â 10 7 white blood cells/mL from healthy donors. Seventyone patients with breast cancer and 107 non-cancer donors consented to provide blood. Results: Based on breast cancer cell lines experiments, HER2 þ CTCs were defined as CTCs with HER2 immunofluorescence intensity ! 3.5 times higher than the CD45 immunofluorescence intensity (100% sensitivity and 99.9% specificity). Among the 71 patients with breast cancer, 31 (43.7%) had HER2 þ tumor. Among the HER2 þ patients, 41.9% (13/31) were found to be HER2 þ based on CTC ! 1, and 25.8% (8/31) were positive based on CTC ! 3. In HER2-negative patients by pathologic examination, 1 (2.5%) patient was found to have ! 3 HER2 þ CTCs, whereas 15 (37.5%) patients had ! 1 HER2 þ CTC. HER2 þ CTCs were detected at all stages, even in early breast cancer, but the detection rate was higher in metastatic breast cancer. Conclusion: This proof-of-concept study strongly suggests that HER2 þ CTCs can be detected using the LiquidBiopsy system.

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Section: Introductionmentioning

confidence: 99%

Detection of HER2-positive Circulating Tumor Cells Using the LiquidBiopsy System in Breast Cancer

Chen

Zhang

Huang

et al. 2019

Clinical Breast Cancer

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“…Furthermore, CTCs measured prior to any new treatment constitute independent prognostic markers that could supplement the currently used clinical predictive biomarkers of breast cancer. It is also noteworthy that predicted disease progression was more accurate when based on measurement of CTC levels after the initiation of therapy, compared to predictions based on levels of tumor markers recommended for monitoring metastatic breast cancer according the international guidelines (e.g., CEA, CA15-3) [51]. This is the first analysis carried out in a large group of patients in Europe, and demonstrates the utility of CTCs in monitoring the progression of distant metastatic breast cancer, and accurately determining the risk of disease progression in a given patient.…”

Section: Clinical Application Of Ctcs: Summarymentioning

confidence: 99%

Circulating tumor cells and their clinical significance

Grzybowska

Fabisiewicz²

2017

Nowotwory. Journal of Oncology

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Metastases to other organs and the formation of secondary tumors are responsible for 90% of cancer-related deaths. However, even in the early stages of cancer, about 30-40% of patients with localized disease may have latent metastasis, which are likely derived from circulating tumor cells (CTCs) involved in disease progression. Therefore, detection and analysis of CTCs can play an important role in the diagnosis and decision-making of adjuvant treatment that aims to prevent metastasis. At present, patients' selection of treatment is based on the statistical risk of recurrence of metastatic disease, without considering whether the tumor cells have spread from the primary tumor. This may lead to unnecessary treatment of non-metastatic disease patients. Therefore, early detection of CTCs in the blood is critically important, and should allow for a more accurate assessment of disease severity. Here, we provide an overview of CTC phenotypes, including plasticity of CTCs, and their clinical significance. NOWOTWORY J Oncol 2017; 67, 4: 243-250

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“…Moreover, detection of CK‐19 mRNA + CTCs after adjuvant chemotherapy is an independent risk factor for shorter DFS ( p < 0.001) and OS ( p = 0.003) . Simply put, detection of CTCs in both early and advanced stage BC can identify patients with worse prognoses than controls (Tables and ). Georgoulias et al .…”

Section: Ctcs May Be Used As a Valuable Prognostic And Predictive Biomentioning

confidence: 99%

“…Moreover, detection of CK-19 mRNA 1 CTCs after adjuvant chemotherapy is an independent risk factor for shorter DFS (p < 0.001) and OS (p 5 0.003). 107 Simply put, detection of CTCs in both early 6,39,104-106,108-115 and advanced 36,[40][41][42][43]46,61,102,103,113,[116][117][118][119][120][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135] stage BC can identify patients with worse prognoses than controls (Tables 2 and 3). Georgoulias et al reported that the paradigm of Herceptin-treated patients based on their and c-erbB2, TFF1, CK19, ERb…”

Section: Ctcs May Be Used As a Valuable Prognostic And Predictive Biomentioning

confidence: 99%

Circulating tumor cells in breast cancer beyond the genotype of primary tumor for tailored therapy

Ren

Han

et al. 2015

Intl Journal of Cancer

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Although TNM staging based on tumor, node lymph status and metastasis status-is the most widely used method in the clinic to classify breast cancer (BC) and assess prognosis, it offers limited information for different BC subgroups. Circulating tumor cells (CTCs) are regarded as minimal residual disease and are proven to have a strong relationship with BC. Detection of 5 CTCs per 7.5 mL in peripheral blood predicts poor prognosis in metastatic BC irrespective of other clinical parameters, whereas, in early-stage BC, detection of CK19 1 CTCs are also associated with poor prognosis. Increasing data and clinical trials show that CTCs can improve prognostic accuracy and help tailor treatment for patients with BC. However, heterogeneous CTCs in the process of an epithelial-mesenchymal transition (EMT) in BC makes it a challenge to detect these rare cells. Moreover, the genotypic and phenotypic features of CTCs are different from primary BC tumors. Molecular analysis of CTCs in BC may benefit patients by identifying those amenable to tailored therapy. We propose that CTCs should be used alongside the TNM staging system and the genotype of primary tumor to guide tailored BC diagnosis and treatment.Breast cancer (BC) is the most common cancer in women in almost every country, including the People's Republic of China. It was the most commonly diagnosed cancer in women in 2013 in the United States and is expected to account for 29% (232,670) of all new cancers in women. 1 Early diagnosis and tumor resection offer the best outcome for patients with BC. Adjuvant chemotherapy and complementary radiotherapy after radical surgery can decrease recurrence risk. 2 However, whether patients with BC benefit from adjuvant treatment is unclear. Therefore, new circulating biological markers are urgently needed to determine patients amenable to adjuvant therapy. Currently, the predominant prognostic system for solid cancers is TNM staging. 3 The TNM staging system is also the most widely used classification for BC to evaluate tumor invasion and prognosis. However, patients with the same TNM stage in BC can have different prognoses, the reasons for which are unclear. As the individualized and precision medicine develops, treatment decisions and prognosis evaluation are more and more based on tumor biology including TNM staging. CTCs are now regarded as new glass leukemia biomarkers for cancer diagnosis and prognosis. CTCs originate from primary tumors, enter the circulatory and lymph node systems and migrate to distant organs to form metastases, which ultimately cause the death of most cancer patients, including patients with BC. 4,5 CTCs can be detected not only in early and advanced stages of patients with BC, but even in early stages of patients with BC that cannot be diagnosed by pathological or conventional imaging methods. 6 Beyond its possibility for

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Clinical significance of circulating tumor cells (CTCs) with respect to optimal cut-off value and tumor markers in advanced/metastatic breast cancer

Abstract: We found that a CTC cut-off value of 1 is appropriate in patients with advanced/metastatic breast cancer. CTCs could yield additional information beyond CEA and CA15-3.

Cited by 25 publications

References 21 publications

Detection of HER2-positive Circulating Tumor Cells Using the LiquidBiopsy System in Breast Cancer

Detection of HER2-positive Circulating Tumor Cells Using the LiquidBiopsy System in Breast Cancer

Circulating tumor cells and their clinical significance

Circulating tumor cells in breast cancer beyond the genotype of primary tumor for tailored therapy

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