Circulating tumour cells in non-metastatic breast cancer: a prospective study

Lucci, Anthony; Hall, Carolyn; Lodhi, Ashutosh; Bhattacharyya, Anirban; Anderson, Amber; Xiao, Lianchun; Bedrosian, Isabelle; Kuerer, Henry Mark; Krishnamurthy, Savitri

doi:10.1016/s1470-2045(12)70209-7

Cited by 478 publications

(358 citation statements)

References 33 publications

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“…9,18 Our results showed that a high proportion of CK 1 /CTCs coexpressed 42 It therefore seemed to be of considerable interest to correlate CK 1 /CD133 1 CTCs with clinicopathological characteristics of BC patients. CK 1 /CD133 1 CTCs were significantly associated with HER2 not amplified and low proliferation index primary tumors suggesting genetic heterogeneity in promoting diversity for the expression of stem cell markers in cancer cells.…”

Section: Discussionmentioning

confidence: 69%

CD133 expression in circulating tumor cells from breast cancer patients: Potential role in resistance to chemotherapy

Nadal

Ortega

Salido

et al. 2013

Intl Journal of Cancer

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CD133 has been associated with cell properties such as self renewal, migration and vasculogenic mimicry, potentially involved in generation of circulating tumor cells (CTCs). We characterized CD133 expression in CTCs of 98 nometastatic breast cancer (BC) patients. CTCs were isolated by immunomagnetic techniques using magnetic beads labeled with a multicytokeratin(CK)-specific antibody (CK3-11D5) and CTCs and CD133 detection through immunocytochemical methods. CK 1 /CD133 1 CTCs were identified in 65% of patients at baseline and 47.8% after systemic therapy (p 5 0.53). Correlation of CD133 status in CTCs with classical clinicopathological characteristics and response to therapy was performed. Her2 not amplified and low Ki-67 index were positively correlated with presence of CK 1 /CD133 1 CTCs. Before any treatment, CK 1 /CD133 1 CTCs were more frequently isolated in patients with luminal BC subtype. No statistically significant differences were found between proportion of CK 1 /CD133 1 CTCs and BC subtypes after systemic therapy, implying a relative enrichment of CK 1 /CD133 1 CTCs in triple negative and HER2-amplified tumors. While CK 1 /CTCs decreases after chemotherapy when analyzing the whole population, CK 1 / CD133 1 CTCs were enriched in post-treatment samples in nonluminal BC subtypes. These findings suggest the potential role of CD133 as a promising marker of chemoresistance in nonluminal BC patients. Further prospective studies and extensive preclinical modeling will be needed to confirm whether CD133 is a marker of resistance to chemotherapy, and its role as a target for novel anticancer therapies targeting cancer stem cells and tumor vasculature.Breast cancer (BC) is a complex and heterogeneous disease comprising multiple tumor entities associated with distinctive different biological feature, clinical behaviors and response to therapy. The current classification of BC is based on the pattern of expression of the hormone receptors (HR) estrogen receptor and/or progesterone receptor, and human epidermal receptor 2 (Her2) that identify three major BC subtypes: luminal tumors, which are HR positive and Her2 negative; Her2 amplified tumors; and those tumors with lack of expression of the three receptors, referred to as triple negative (TN) BC. 1 Despite advances in BC treatments, primary and acquired resistance to cancer therapies remains a challenge especially in nonmetastatic patients. Cancer stem cells (CSC) have been

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Section: Discussionmentioning

confidence: 69%

CD133 expression in circulating tumor cells from breast cancer patients: Potential role in resistance to chemotherapy

Nadal

Ortega

Salido

et al. 2013

Intl Journal of Cancer

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“…A prospective study of 302 patients with nonmetastatic breast cancer showed that ≥1 CTC/7.5 ml was a predictor of poorer PFS and OS (Lucci et al, 2012). A similar result was obtained in a large prospective trial using the CellSearch system in patients with breast cancer (Rack et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of circulating tumor cells in patients with ampullary cancer

Sun

Liang

Wang

et al. 2018

Journal Cellular Physiology

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Circulating tumor cells (CTCs) are an important topic of investigation for both basic and clinical cancer research. In this prospective study, we evaluated the clinical role of CTCs in ampullary cancer. We analyzed blood samples from 62 consecutively diagnosed patients with ampullary adenocarcinoma and 24 healthy controls for their CTC content. Combined data from immunostaining of CD45, 4′,6‐diamidino‐2‐phenylindole (DAPI), and fluorescence in situ hybridization with a chromosome 8 centromere (CEP8) probe were used to identify CTCs; cells that were CD45‐/DAPI+/CEP8>2 were considered CTCs. The Cox proportional hazards model was used to assess the relationship between CTCs, clinical characteristics, and patient outcomes. We detected ≥2 CTCs/3.2 ml whole blood in 43 of 62 patients (69.4%), as well as ≥5 CTCs/3.2 ml in 16 of these patients (25.8%). A CTC cutoff value of 2 cells/3.2 ml achieved 69.4% sensitivity and 95.8% specificity as a diagnostic tool; CTCs were associated with tumor burden. CTC levels ≥3/3.2 ml (hazard ratio [HR]: 2.5, 95% confidence interval [CI]: (1.2–5.2), p = 0.014) and ≥5/3.2 ml (HR: 3.5, 95% CI: 1.7–7.3, p < 0.001) were both associated with shorter disease‐free survival. Moreover, ≥3 CTCs/3.2 ml (HR: 2.7, 95% CI: 1.2–6.3, p = 0.019) and ≥5 CTCs/3.2 ml (HR: 3.8, 95% CI: 1.8–8.5, p < 0.001) were predictive of shorter overall survival. CTC assessment may help identify patients with ampullary cancer who are at high risk of an unfavorable outcome.

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“…Various thresholds have been used in studies examining the predictive performance of CTC in metastatic breast and metastatic prostate cancer (≥5 CTC/7.5mL blood) 6,8,11 versus metastatic colorectal cancer (≥3 CTC/7.5 mL blood). 9 There is also a precedent for the use of CTC thresholds of ≥1 or ≥2 in studies of nonmetastatic breast cancer and bladder cancer, 5,7,10 although it is notable that at least one study 7 collected three 8-10 mL tubes of peripheral blood in order to detect these rare cells. In order to compare the prognostic performance of CTC at different CTC cutoffs, we elected to show results with cutoffs of both CTC ≥5 and CTC ≥2.…”

Section: Discussionmentioning

confidence: 99%

“…6 CTC enumeration has also been shown to have prognostic utility in patients with nonmetastatic breast cancer. 5 A large German study with 2,026 patients with early breast cancer showed that CTC ≥1 is an independent predictor of poor disease-free survival, breast cancer-specific survival, and overall survival; the worst prognosis was found in patients with CTC ≥5. 7 Similar results have been shown for metastatic colon, prostate and other cancers.…”

Section: Discussionmentioning

confidence: 99%

“…4 It is designed to capture cells expressing cancer specific epithelial cell adhesion molecules (EpCAM) using antibody-coated magnetic beads followed by positive identification of intact tumor cells using fluorescently labeled antibodies against cytokeratin and nuclear staining. Detection of CTC in blood has been associated with poor progression free and overall survival in patients with metastatic/non-metastatic breast cancer [5][6][7][8] , metastatic colon cancer, 9 and bladder cancer. 10 CTC were also reported to be associated with overall survival in patients with metastatic castration-resistant prostate cancer and have been shown to be detectable in patients with other metastatic cancers including ovarian and lung cancers.…”

Section: Introductionmentioning

confidence: 99%

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