Serum HER-2 Extracellular Domain: Relationship with Clinicobiological                     Presentation and Prognostic Value before and after Primary Treatment in 701                     Breast Cancer Patients

Saghatchian, M.; Guepratte, S.; Hacène, K.; Neumann, Rainer; Floiras, J.-L.; Pichon, M.

doi:10.1177/172460080401900102

Cited by 17 publications

(5 citation statements)

References 20 publications

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“…A number of breast cancer studies demonstrated that elevated serum HER 2 ECD is associated with high grade tumour, larger tumour burden, lymph node involvement, higher recurrence rate and higher mortality, thus, it was associated with a poorer prognosis [9], [22], [23]. In our study, elevated levels of HER 2 ECD were also strongly associated with liver metastasis and high tumour load (multiple metastases and increased LDH levels).…”

Section: Discussionsupporting

confidence: 67%

Serum HER 2 Extracellular Domain Level Is Correlated with Tissue HER 2 Status in Metastatic Gastric or Gastro-Oesophageal Junction Adenocarcinoma

Dai

Wang

et al. 2013

PLoS ONE

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BackgroundTo explore the association between serum human epidermal growth factor receptor 2 (HER 2) extracellular domain (ECD) levels and tissue HER 2 status in metastatic gastric cancer.Patients and MethodsHER 2 status was retrospectively analyzed in 219 advanced gastric or gastroesophageal junction (GEJ) patients. Serum HER 2 ECD was measured by chemiluminescent assay and tissue HER 2 was assessed by fluorescent in situ hybridisation (FISH) and immunohistochemistry (IHC) assay.ResultsSignificant associations were found between serum HER 2 ECD levels and tissue HER 2 status. Twenty-four patients had HER 2 ECD levels >16.35 ng/mL, which has a sensitivity of 51.4% and a specificity of 97.3% to predict tissue HER 2 status. When the cut-off value was increased to 22 ng/mL, then all 12 patients with serum HER 2 ECD levels>22 ng/mL were tissue HER 2 positive, corresponding to a specificity of 100% and a sensitivity of 32.4%. High serum HER 2 ECD levels were strongly associated with the intestinal histological type (Lauren’s classification), liver metastasis, multiple metastasis (>2) and increased LDH levels, but not with overall survival.ConclusionsThe high specificity of the serum HER 2 ECD assay in predicting tissue HER 2 status suggests its potential as a surrogate marker of the HER 2 status in gastric cancer.

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Section: Discussionsupporting

confidence: 67%

Serum HER 2 Extracellular Domain Level Is Correlated with Tissue HER 2 Status in Metastatic Gastric or Gastro-Oesophageal Junction Adenocarcinoma

Dai

Wang

et al. 2013

PLoS ONE

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“…The results of sHER2 levels were moderately concordant with tissue HER2 status by IHC or FISH (82.3%). In previous studies, elevated sHER2 levels were observed in 4.4–14.2% of operable breast cancer patients [ 4 , 14 , 15 , 18 , 20 , 21 ]. Ludovini et al reported that the sensitivity of sHER2 levels for tissue HER2 status was 38.1% and the concordance rate was 87.1%, similar to our results [ 18 ].…”

Section: Discussionmentioning

confidence: 98%

The Significance of Serum HER2 Levels at Diagnosis on Intrinsic Subtype-Specific Outcome of Operable Breast Cancer Patients

et al. 2016

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PurposeThis study evaluated the association of serum HER2 (sHER2) levels at diagnosis with clinicopathologic parameters and disease free survival (DFS) in operable breast cancer patients according to intrinsic subtype.MethodsThe sHER2 levels were measured using a chemiluminescence immunoassay. The HER2 status in all tumor tissues was determined by immunohistochemistry, and confirmed in equivocal cases by fluorescence in situ.ResultsThere were 436 consecutive stage I-III breast cancer patients with sHER2 result at diagnosis between Nov 2004 and Dec 2011. High sHER2 levels (≥ 15 ng/ml) were reported in 52 patients (11.9%) and HER2 overexpression in tumor tissue was observed in 111 patients (25.5%). High sHER2 levels were associated significantly with advanced stage (P < 0.001), mastectomy (P = 0.012), neoadjuvant chemotherapy (P < 0.001), anti-HER2 therapy (P < 0.001) and hormone therapy (P = 0.022). The patients with high sHER2 levels had a worse DFS (P < 0.001). In multivariate analysis, high sHER2 levels were associated significantly with worse DFS (HR = 2.25, 95% CI 1.27–3.99, P = 0.005). High sHER2 levels were associated with worse DFS in the HR+/HER2-, HR+/HER2+ and HR-/HER2+ subtypes (P = 0.043, 0.003 and 0.041, respectively).ConclusionsThese results show that the sHER2 level at diagnosis is a useful prognostic factor in patients with operable breast cancer, especially in the HR+/HER2-, HR+/HER2+ and HR-/HER2+ subtypes.

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“…For example, in HER2 over-expressing breast cancer, anti-HER2 antibodies could be utilized to remove HER2 expressing exosomes as well as soluble HER2, which is proteolytically cleaved from the cancer cell surface and also neutralizes the activity of Herceptin® [135]. Several studies reveal that high levels of shed HER2 are associated with high-grade tumors, lymph node metastasis, and higher mortality of breast cancer patients [136-138]. Thus, the capability for simultaneously removing both soluble and exosome associated oncoproteins using the ADAPT™ system could offer a unique strategy for improving the therapeutic outcomes for cancer patients.…”

Section: Extracorporeal Hemofiltration Of Circulating Factors As a Thmentioning

confidence: 99%

Exosome removal as a therapeutic adjuvant in cancer

et al. 2012

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Exosome secretion is a notable feature of malignancy owing to the roles of these nanoparticles in cancer growth, immune suppression, tumor angiogenesis and therapeutic resistance. Exosomes are 30–100 nm membrane vesicles released by many cells types during normal physiological processes. Tumors aberrantly secrete large quantities of exosomes that transport oncoproteins and immune suppressive molecules to support tumor growth and metastasis. The role of exosomes in intercellular signaling is exemplified by human epidermal growth factor receptor type 2 (HER2) over-expressing breast cancer, where exosomes with the HER2 oncoprotein stimulate tumor growth and interfere with the activity of the therapeutic antibody Herceptin®. Since numerous observations from experimental model systems point toward an important clinical impact of exosomes in cancer, several pharmacological strategies have been proposed for targeting their malignant activities. We also propose a novel device strategy involving extracorporeal hemofiltration of exosomes from the entire circulatory system using an affinity plasmapheresis platform known as the Aethlon ADAPT™ (adaptive dialysis-like affinity platform technology) system, which would overcome the risks of toxicity and drug interactions posed by pharmacological approaches. This technology allows affinity agents, including exosome-binding lectins and antibodies, to be immobilized in the outer-capillary space of plasma filtration membranes that integrate into existing kidney dialysis systems. Device therapies that evolve from this platform allow rapid extracorporeal capture and selective retention of target particles < 200 nm from the entire circulatory system. This strategy is supported by clinical experience in hepatitis C virus-infected patients using an ADAPT™ device, the Hemopurifier®, to reduce the systemic load of virions having similar sizes and glycosylated surfaces as cancer exosomes. This review discusses the possible therapeutic approaches for targeting immune suppressive exosomes in cancer patients, and the anticipated significance of these strategies for reversing immune dysfunction and improving responses to standard of care treatments.

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Serum HER-2 Extracellular Domain: Relationship with Clinicobiological Presentation and Prognostic Value before and after Primary Treatment in 701 Breast Cancer Patients

Cited by 17 publications

References 20 publications

Serum HER 2 Extracellular Domain Level Is Correlated with Tissue HER 2 Status in Metastatic Gastric or Gastro-Oesophageal Junction Adenocarcinoma

Serum HER 2 Extracellular Domain Level Is Correlated with Tissue HER 2 Status in Metastatic Gastric or Gastro-Oesophageal Junction Adenocarcinoma

The Significance of Serum HER2 Levels at Diagnosis on Intrinsic Subtype-Specific Outcome of Operable Breast Cancer Patients

Exosome removal as a therapeutic adjuvant in cancer

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