Serum HER2 Levels Research Articles

Serum HER2 Level Predicts Therapeutic Efficacy and Prognosis in Advanced Breast Cancer Patients.

The purpose of this study was to investigate the therapeutic efficacy and prognosis of serum HER2 (sHER2) in patients with advanced breast cancer. We analyzed the sHER2 levels of 200 patients with advanced breast cancer receiving first or second line treatment, the tissue HER2 (tHER2) level was also analyzed. Indicators of therapeutic efficacy and prognosis were objective response rate (ORR), disease control rate (DCR), and time to progression (TTP). The baseline sHER2 level was high in 132 patients and low in 68 patients. The high level of sHER2 is correlated with molecular subtype (p=0.016), visceral metastasis (p<0.001), liver metastasis (p<0.001), tissue HER-2 (tHER2) (p=0.001), and, among tHER2-low tumors (59 patients), the baseline sHER2 high level was associated with a higher proportion of brain metastasis. The ORR of patients with baseline sHER2 high level is higher than those with baseline sHER2 low level (p=0.026). The TTP of patients with baseline sHER2 low level is longer than the patients with baseline sHER2 high level (p=0.024). For patients with baseline sHER2 high level, a significant decrease in sHER2 after two cycles of treatment indicates higher ORR, DCR, and an extension of TTP. After multiple cycles of treatment, for patients with tHER-2 positive and baseline sHER2 high level, the DCR in the sHER2 decrease in the negative group was higher than that in the continuous positive group (p=0.037). Patients with a rapid decline type of sHER2 dynamic change curve had higher ORR and prolonged TTP compared with patients with other types of sHER2 dynamic change curve. There is no correlation between OS and sHER2 levels. Our study showed that patients with advanced breast cancer had a high level of sHER2 at recurrence, regardless of whether they are tHER2 positive or negative. Dynamic detection of sHER2 can help predict therapeutic efficacy and prognosis, regardless of whether tHER-2 is positive or negative.

Serum HER2 Level Predicts Therapeutic Efficacy and Prognosis in Advanced Breast Cancer Patients [Letter

Serum HER2 Level Predicts Therapeutic Efficacy and Prognosis in Advanced Breast Cancer Patients [Letter

Evaluation of the influence of trastuzumab therapy on serum levels of HER-2 protein and breast cancer cell lines.

Breast cancer is a complex disease characterised by abnormal cell growth in breast tissue. Trastuzumab is a targeted therapy that inhibits the HER-2 receptor and suppresses tumour growth. We aimed to determine if the clinical course of the disease could be predicted by early changes in serum levels of human epidermal growth factor receptor 2 (HER-2/neu) following trastuzumab-based therapy. The study enrolled 120 women, divided into an experimental group (60 breast cancer patients receiving trastuzumab) and a control group (60 healthy women). Serum samples were collected before each weekly trastuzumab treatment. In addition, human breast cancer cell lines MCF-7 and AMJ13 were cultured in vitro and treated with trastuzumab. The study assessed cell viability using a cytotoxicity assay (methyl thiazolyl tetrazolium) and measured HER-2 protein levels. The half maximal inhibitory concentration (IC50) was determined to evaluate the effect of trastuzumab on breast cancer. The results showed that breast cancer patients had significantly lower serum levels of HER-2 compared to the control group. The cytotoxicity assay demonstrated that increasing trastuzumab concentration enhanced growth inhibition and cytotoxicity in the cell lines. There was a significant difference in IC50 between the MCF-7 and AMJ13 cell lines. The study provides valuable insights into the effects of trastuzumab on serum HER-2 levels and breast cancer cell lines. These findings have implications for resource allocation and treatment decisions in breast cancer management. By understanding the impact of trastuzumab on HER-2 levels and tumour cells, healthcare professionals can make more informed decisions regarding therapy options for patients.

Study the technical validity and feasibility of serum HER-2/Neu and its correlation with tissue HER-2 status in female breast cancer patients only

Background: Breast cancer is one of the leading causes of death in women worldwide. The future burden of breast cancer is predicted to increase over 3 million new cases and 1 million deaths in 2040. In India, it is being increasingly diagnosed at a younger age as compared to the west. Human epidermal growth factor receptor 2 (HER-2) transmembrane protein, with a molecular weight 185 kDa, plays a key role in cell growth and its overexpression favors cell proliferation by inhibiting apoptosis. HER-2 extracellular domain, released into blood before appearing into tissue, can be easily detected by enzyme-linked immunosorbent assay (ELISA) using serum. HER-2 has many roles in assisting diagnosis, targeted therapy, and evaluating prognosis. Aims and Objectives: The study aimed to monitor the serum HER-2 level and its correlation with tissue HER-2 status in breast cancer patients. Materials and Methods: We performed a prospective study on technical validity and feasibility of serum HER-2 level by ELISA in breast cancer patients and its correlation with tissue HER-2 status by immunohistochemistry (IHC) method. Results: We found the serum ELISA level was raised and within the reference range in all breast cancer patients. A higher level of serum HER-2 level was seen in high tumor stage, high Nottingham grade, and with axillary lymph node metastasis. Serum HER-2 level was significantly higher in IHC score 3+ as compared to score 2+and 1+. Conclusion: This study concluded that serum HER-2 ELISA is a valid and feasible test. Association of serum HER-2 level with tumor stage; Nottingham grade; and axillary nodal metastasis was significant. The correlation between serum HER-2 and tissue HER-2 was found significant. Thus, serum HER-2 may be used as an early diagnostic and prognostic biomarker to guide in clinical practice.

A multicenter phase II study of vaccines to prevent recurrence in patients with HER-2–positive breast cancer.

532 Background: Patients (pts) with early stage HER2-positive breast cancer are commonly treated with neoadjuvant HER2-targeted therapy. Pts who have residual invasive disease have a less favorable outcome and increased risk of recurrent disease than pts with a complete pathologic response (pCR). It also has been observed that pts who do not achieve a pCR have low or absent anti-HER-2 CD4 Th1 responses. We hypothesized that correcting anti-HER-2 CD4 Th1 response using vaccines will be safe, induce anti-tumor immunity in HER2-positive breast cancer and reduce the risk of recurrence. We conducted a multi-center, phase 2, randomized study to determine the safety, immunogenicity and recurrence free survival of two HER2 vaccines (multivalent anti-oncodriver DNA vaccine (WOKVAC) or HER-2-pulsed dendritic cell vaccine (DC1)). Methods: Pts with HER2-positive early breast cancer were eligible if they had residual invasive disease at surgery after receiving neoadjuvant chemotherapy plus HER2-targeted therapy. Patients were randomly assigned in a 1:1 ratio, with stratification according to residual cancer burden (RCB) (1+2 vs 3) to receive adjuvant HER2 vaccination with either DC1 or WOKVAC. For the initial vaccination phase, DC1 was delivered via US guided inguinal lymph node administration, weekly x 6 weeks and WOKVAC was given intradermally on weeks 1, 4, and 7. Booster vaccines were given at months 6, 9 and 12. The primary end point is to evaluate the safety and tolerability of each vaccine and assess immune response rate as measured by ELISPOT. Each treatment arm will be assessed separately. Secondary endpoints include recurrence-free survival. Exploratory analyses include the assessment of prognostic and predictive biomarkers including circulating tumor cells, serum HER2 levels, and other immune correlative biomarkers. Here we are reporting the initial safety results. Results: Total of 110 eligible pts (55 WOKVAC vs 55 DC1) were enrolled from 2/2018 to 12/2022 and received at least one dose of treatment and 38 pts pending completion of the booster phase. Most pts had clinical stage II/III 56/35 (82%) and 50% had positive node disease at diagnosis. 82% had hormone receptor positive disease. 37/38/8 patients had RCB 1/2/3. For patients without known RCB status, ypTNM was used to randomize (yp stage I/II/III = 13/13/1 pts). The most frequently observed treatment related adverse events (TRAE) were injection site pain/reaction (38%) and chills (34%), fever (25%) and fatigue (40%) for DC1 arm. For WOKVAC, the most common toxicities included injection site reaction (68%) and fatigue (37%). All of these were grade 1 and 2. Nine patients had events including new primary cancer (1), local recurrence (2), metastatic disease recurrence (6). Conclusions: Both DC1 and WOKVAC HER2 vaccines were well tolerated without significant toxicities. Updated results will be presented at the meeting including correlatives. Clinical trial information: NCT03384914 .

Healthy Male Individuals Possess Higher Plasma HER-2 Level than Females.

Considering HER2 as one of the well-known biomarkers in the cancer field, and published articles regarding serum levels of HER2, in this paper we tried to highlight the issue that most studies don't stratify the HER-2 concentration of individuals in terms of gender. In this brief survey, healthy individuals with no prior non-communicable diseases were categorized as males (n=34) and females (n=43), and all samples were evaluated for plasma HER-2 levels at once. Surprisingly, the plasma level of HER-2 of healthy male individuals (mean= 2.28 ± 0.21 ng/mL) was significantly (P<0.0001) higher than the plasma level of HER-2 of healthy females (mean: 0.06 ± 0.09 ng/mL), with no overlap. Therefore, we suggest that more studies are required to re-check the cutoff values for HER-2 plasma levels based on gender since the clinical implications of a unique HER-2 cutoff for both genders may be seriously concerning.

Covalent Hemin/G4 complex-linked sandwich bioassay on magnetic beads for femtomolar HER-2/neu detection in human serum via direct electrocatalytic reduction of oxygen

Liquid biopsy assays for tumour biomarkers circulating in blood are perspective non-invasive tools for cancer diagnosis and treatment monitoring. Here, we suggest a simple, 1 h long electrochemical DNAzyme-linked aptamer- and immuno-sandwich magnetic assay for analysis of serum HER-2/neu protein overexpressed in several aggressive cancers. In the assay, we used a covalent hemin-guanine quadruplex (G4) complex as a novel O2-dependent electrocatalytic label that allowed 10 fM (aptamer-aptamer) and 1 fM (aptamer-antibody) detection of HER-2/neu in human serum. The O2 reactivity of the aptamer-conjugated label was detected at high-surface-area graphite electrodes displaying a high efficiency of O2 reduction electro-catalyzed by this DNAzyme. In contrast to the recognised H2O2 reactivity, the O2 reactivity of the covalent hemin/G4 complex depended only on ambient O2 present in solutions, and did not require adding such traditional reagents as hemin and H2O2, and solution de-aeration. Human serum albumin, urokinase plasminogen activator and thrombin did not interfere, and the assay was used for analysis of basal serum levels of HER-2/neu. Due to the simplicity and low cost, sandwich assays exploiting O2-linked electrocatalysis by the covalent hemin-G4 complexes represent a more advanced electrochemical ELISA platform for ultrasensitive and fast detection of low concentrations of proteins in complex biological matrices.

Abstract OT1-16-01: A multicenter phase II study of vaccines to prevent recurrence in patients with HER-2 positive breast cancer

Abstract Background: HER2-positive breast cancer patients are commonly treated with neoadjuvant therapy including HER2-targeted therapy. Patients who have residual invasive disease have less favorable outcomes with an increased risk of recurrent disease than patients with complete pathologic response (pCR). It has also been observed that these non-pCR patients have low or absent anti-HER-2 CD4 Th1 responses. We hypothesized that correcting the anti-HER-2 CD4 Th1 response using vaccines will increase interferon gamma production which we have shown is a potent inducer of apoptosis and senescence in HER2-positive breast cancer. This study will be evaluating safety and immunogenicity of two vaccines (multivalent anti-oncodriver DNA vaccine (WOKVAC) or HER-2-pulsed dendritic cell vaccine (DC1)). Methods: This is a multi-center, phase 2, randomized study to determine the safety and tolerability of HER2 vaccines (DC1 and WOKVAC), assess immunogenicity, and evaluate recurrence free survival. Patients with HER2-positive early breast cancer (stage I-III) are eligible if they have residual invasive disease in the breast or axilla at surgery after receiving neoadjuvant chemotherapy plus HER2 -targeted therapy. Patients are randomly assigned in a 1:1 ratio to receive 1 of 2 adjuvant HER2 vaccines, either DC1 or WOKVAC for 1 year. A permuted-block randomization scheme was used with stratification according to residual cancer burden (RCB) (1+2 vs 3). The primary end points are safety and immunogenicity (immune response rate measured by ELISPOT). Each treatment arm will be assessed separately. Any statistical comparison between arms is purely exploratory, as this study is neither designed nor powered for comparative hypotheses. Secondary endpoints include recurrence-free survival. Exploratory analyses include the assessment of prognostic and predictive biomarkers including circulating tumor cells, serum HER2 levels, and other immune markers. The enrollment began in 2018 and we plan to accrue the total of 110 patients. ClinicalTrials.gov Identifier: NCT03384914 Citation Format: Hyo S Han, Mary Disis, Robert Wesolowski, Carla Fisher, Shipra Gandhi, Nancy Chan, William Gwin, Keerthi Gogineni, Rosemarie Mick, Christina Sierra Rodriguez, Deanna Hogue, Hien Liu, Ricardo Costa, Brian Czerniecki. A multicenter phase II study of vaccines to prevent recurrence in patients with HER-2 positive breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-16-01.

Expression of HER2/neu in gastric adenocarcinoma and its correlation with serum HER2/neu level and E-cadherin expression.

: To assess HER2/neu expressions and correlate with E-cadherin and Serum HER2 level in gastric carcinoma. 31 gastric biopsies and 1 resected specimen were taken in the study with patient details and stained with H and E for histopathological details following Lauren's classification. Immunohistochemistry for HER2 and E-cadherin expression was conducted followed by serum HER2/neu ELISA. Adenocarcinoma with 61% diffuse, 29% intestinal, and 10% other type were observed with predominant HER2 immunoexpression in intestinal-type than in diffuse-type adenocarcinoma. Other observations marked 44% as 3+/positive and 56% as 2+/equivocal in intestinal type while 26% cases as 3+/positive, 69% as 2+/equivocal, and 1% as 1+/negative were observed in diffuse type. The data presented 33% membranous positivity and 67% both membranous + cytoplasmic positivity in intestinal type while 2% showed membranous positivity, 47% both membranous + cytoplasmic, and 42% only cytoplasmic positivity in diffused type. On comparing the localization pattern of HER2 and E-cadherin, 25% of cases showed membranous staining while 50% of cases showed membranous with cytoplasmic staining for both. No cytoplasmic HER2 staining as well as no any staining for E-cadherin was shown by 6% cases. Thus, it can be concluded that cytoplasmic expression of HER2 in gastric adenocarcinoma (mainly diffuse type) may be due to shedding of its extracellular domain, leading to loss of membranous E-cadherin expression on immunohistochemistry. The loss of membranous expression of E-cadherin and increased serum HER2 ELISA were correlated well with these findings.

A Scoping Review: Clinical Trials Assessing Turmeric Dietary Supplement Use in Cancer

Turmeric, one of the top selling botanicals in the United States, has been identified by our research group as the top botanical dietary supplement used by women diagnosed with breast cancer (22%, n = 1,224), with health care providers, family/friends and social media all being frequently reported sources of information regarding its use. However, some scientists have questioned whether curcumin(oids), the primary turmeric-derived component in these supplements, have medicinal benefits, in part due to their poor bioavailability, despite a history of medicinal turmeric use for thousands years in Ayurvedic medicine. A scoping review of the literature was therefore undertaken to identify clinical trials investigating the validity of oral curcumin-containing turmeric DS. Using a defined search strategy, eight databases were reviewed (thru 5/29/2019), identifying n =4767 potential reports for inclusion, from which only n = 315 remained after review by three independent observers. Cancer was among the most commonly studied disorders (n = 40), which also included disorders of glucose and lipid metabolism (n = 69), musculoskeletal disorders (n= 50), and gastrointestinal and hepatic disorders (n = 50). Prostate (n = 8), gastrointestinal (n = 11), and breast (n = 6) were among the most commonly studied cancers. In addition to differences and some weaknesses in study design, the variability and, in some cases, a lack of clarity as to the composition of the natural products tested make it difficult to derive solid conclusions related to clinical use for oncology. Despite these limitations, most oncologic and non-oncologic clinical trials reported significant physiologic effects. Reduced HER2 serum levels; reduced serum/urine protein, paraprotein, and creatinine levels in patients with myelomatous disease; reduced urinary symptoms in prostate cancer patients; reduced inflammatory markers; and improved quality of life in an array of malignant neoplastic syndromes are among some of the findings in these clinical studies. In addition, curcumin also caused increased muscle and adipose tissue wasting in cachexic patients with pancreatic cancer. These varying results, both positive and negative, combined with the popularity of curcumin DS in the United States, including by women with breast cancer, provide evidence that further large, well-designed human trials should not be abandoned. This is particularly true for oncologic populations at higher risk of possible untoward effects related to drug-supplement interactions.

Serum HER2 levels predict treatment efficacy and prognosis in patients with HER2-positive breast cancer undergoing neoadjuvant treatment.

Controversy remains regarding the predictive and prognostic value of serum human epidermal growth factor receptor 2 (HER2) in breast cancer. The purpose of this retrospective study was to determine the clinical utility and efficacy of serum HER2 (sHER2) in predicting treatment response and prognosis in patients with HER2-positive breast cancer undergoing neoadjuvant chemotherapy and trastuzumab treatment. A total of 309 HER2-positive breast cancer patients diagnosed at Fudan University Shanghai Cancer Center from July 2015 to January 2019 were analyzed. Baseline sHER2 levels were obtained for all patients and sHER2 levels were collected after 2 cycles of treatment in 208 patients. A sHER2 level ≥15 ng/mL was regarded as "high expression" and sHER2 <15 ng/mL was regarded as "low expression". Outcome measures of treatment efficacy and prognosis were pathological complete response (pCR) and invasive disease-free survival (iDFS), respectively. In patients with high baseline sHER2, more were ER-negative (P=0.029), had larger tumor size (P=0.006), more advanced clinical stage (P=0.002), higher Miller-Payne grade (P=0.024) and higher likelihood of iDFS events (P=0.015). Patients with high sHER2 levels after 2 cycles of treatment had lower pCR rates (P=0.038), higher Miller-Payne grade (P=0.013) and higher likelihood of iDFS events (P=0.003). Kaplan-Meier analysis showed significant differences in iDFS between patients with high and low sHER2 levels at baseline (P=0.019) and after 2 cycles of treatment (P=0.000). Further analyses according to cancer subtypes found baseline sHER2 to be significantly correlated with the iDFS of Luminal B patients (p=0.002), while sHER2 levels after 2 cycles of treatment was significantly correlated with the iDFS of HER2-enriched patients (P=0.000). Univariate analysis showed significant association between iDFS and tumor size (P=0.026), lymph node status (P=0.008), clinical stage (P=0.031), baseline sHER2 (P=0.024), overall tumor response (P=0.011), pCR (P=0.043) and Miller-Payne grade (P=0.001). Multivariate analysis found Miller-Payne grade (P=0.037) to be significantly associated with iDFS. Our results demonstrate the clinical value of sHER2 in a population of Chinese breast cancer patients, suggesting that sHER2 levels after 2 cycles of neoadjuvant therapy may be more predictive of treatment outcomes and that the prognostic value of sHER2 may be time point and subtype dependent.

Correlation of Serum HER-2/neu Levels with Clinico-Pathological Variables and Tissue Immunohistochemistry in Breast Carcinoma

Introduction: Serum levels of HER-2/neu protein is raised in primary as well as metastatic breast cancer and decreased serum HER-2/neu concentration in patients treated with HER- 2/neu inhibitors like trastuzumab is a good prognostic indicator in metastatic cases. Aims: To evaluate the concordance of serum HER-2/neu concentration with tissue HER-2/neu immunohistochemistry and determine its relationship with various prognostic indicators like age, size of tumour, lymph node status, grade, and stage of tumour. Materials and methods: The preoperative serum samples of 56 clinically and cytologically diagnosed cases of breast carcinoma were taken and postoperative mastectomy specimens were examined for the histologic type, lympho-vascular invasion, stage, and grade of the tumour. Immunohistochemical study of HER-2/neu xpression and HER-2/neu serum biochemistry was studied. Results: Age of the patients ranged from 25-75 years. Twenty-three cases (41.1%) were premenopausal while 33 cases (58.9%) postmenopausal. Forty-seven cases (83.9%) were of the infiltrating ductal carcinoma (NOS) type. Serum positivity for HER-2/neu was noted in 29 (51.8%) cases. Serum HER-2/neu levels showed a positive correlation with increase in tumour size, grade, stage of tumour and lymph node involvement. Serum HER-2/neu positivity was seen in 20 (68.9%) IHC positive patients and 9 (33.3%) IHC negative patients, with a statistically significant correlation (p=0.005). Conclusions: Serum HER-2/neu levels directly correlate with prognostic factors like tumour size, grade, stage of the tumour and lymph node metastasis and can be used as a complimentary tool to tissue HER-2/neu immunohistochemistry.

Diagnostic value of serum HER2 levels in breast cancer: a systematic review and meta-analysis

BackgroundMeasurement of serum human epidermal growth factor receptor-2 (HER-2/neu) levels might play an essential role as a diagnostic/screening marker for the early selection of therapeutic approaches and predict prognosis in breast cancer patients. We aimed to undertake a systematic review and meta-analysis focusing on the diagnostic/screening value of serum HER-2 levels in comparison to routine methods.MethodsWe performed a systematic search via PubMed, Scopus, Cochrane-Library, and Web of Science databases for human diagnostic studies reporting the levels of serum HER-2 in breast cancer patients, which was confirmed using the histopathological examination. Meta-analyses were carried out for sensitivity, specificity, accuracy, area under the ROC curve (AUC), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR).ResultsFourteen studies entered into this investigation. The meta-analysis indicated the low sensitivity for serum HER2 levels (Sensitivity: 53.05, 95%CI 40.82–65.28), but reasonable specificity of 79.27 (95%CI 73.02–85.51), accuracy of 72.06 (95%CI 67.04–77.08) and AUC of 0.79 (95%CI 0.66–0.92). We also found a significant differences for PPV (PPV: 56.18, 95%CI 44.16–68.20), NPV (NPV: 76.93, 95%CI 69.56–84.31), PLR (PLR: 2.10, 95%CI 1.69–2.50) and NLR (NLR: 0.58, 95%CI 0.44–0.71).ConclusionOur findings revealed that although serum HER-2 levels showed low se nsitivity for breast cancer diagnosis, its specificity, accuracy and AUC were reasonable. Hence, it seems that the measurement of serum HER-2 levels can play a significant role as a verification test for initial negative screening test results, especially in low-income regions due to its cost-effectiveness and ease of implementation.

Monitoring Value of Serum HER2 as a Predictive Biomarker in Patients with Metastatic Breast Cancer.

PurposeThe aim of this study was to investigate the monitoring value of serum HER2 in patients with metastatic breast cancer.Patients and MethodsWe firstly evaluated the association of serum HER2 levels with tissue HER2 expression and imaging results in 420 breast cancer patients admitted into Tianjin Medical University Cancer Institute and Hospital between April 2016 and December 2018. Secondly, we analyzed serum HER2 levels in breast cancer patients with different metastatic degrees.ResultsThere is a higher correlation between serum HER2 and tissue HER2 in breast cancer patients with stage III (κ=0.670, p<0.001) and stage IV (κ=0.464, p<0.001). Serum HER2 levels were significantly associated with imaging results (κ=0.478, p<0.001). The ROC curve analysis showed that serum HER2 was superior to other serum markers for predicting metastatic breast cancer. Multinomial logistic regression revealed that the patients with higher serum HER2 levels would be more likely to have breast cancer metastasis.ConclusionSerum HER2 levels in breast cancer patients can partly reflect tissue HER2 expression and tumor imaging changes, and serum HER2 may be used as a biomarker for evaluating metastatic status in patients with breast cancer.

Association between serum HER2/ErbB2 levels and coronary artery disease: a case\u2013control study

BackgroundResearch has associated human epidermal growth factor receptor (HER2) with glucose and lipid metabolism. However, the association between circulating HER2 levels and coronary artery disease (CAD) remains to be elucidated.MethodsWe performed a case–control study with 435 participants (237 CAD patients and 198 controls) who underwent diagnostic coronary angiography from September 2018 to October 2019. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for CAD were calculated with multiple logistic regression models after adjustment for confounders.ResultsOverall, increased serum HER2 levels were independently associated with the presence of CAD (OR per 1-standard deviation (SD) increase: 1.438, 95% CI 1.13–1.83; P = 0.003) and the number of stenotic vessels (OR per 1-SD increase: 1.399, 95% CI 1.15–1.71; P = 0.001). In the subgroup analysis, a significant interaction of HER2 with body mass index (BMI) on the presence of CAD was observed (adjusted interaction P = 0.046). Increased serum HER2 levels were strongly associated with the presence of CAD in participants with BMI ≥ 25 kg/m2 (OR per 1-SD increase: 2.143, 95% CI 1.37–3.35; P = 0.001), whereas no significant association was found in participants with BMI < 25 kg/m2 (OR per 1-SD increase: 1.225, 95% CI 0.90–1.67; P = 0.201).ConclusionElevated HER2 level is associated with an increased risk of CAD, particularly in people with obesity. This finding yields new insight into the pathological mechanisms underlying CAD, and warrants further research regarding HER2 as a preventive and therapeutic target of CAD.

20P - Diagnostic value of serum HER-2 level in compression with tissue HER-2 in breast cancer: A systematic review and meta-analysis

BackgroundMeasurement of serum human epidermal growth factor receptor-2 (HER-2/neu) levels for breast cancer is still controversial and not recommended in any clinical procedures. However, it seems that HER-2 measuring can plays an important role as a diagnostic marker for early selection of therapeutic approach as well as predict of prognosis in breast cancer patients. We aimed to undertake a systematic review and meta-analysis focuses on the diagnostic value of serum HER-2 level measures by ELISA in compare to other methods due to its ease of implementation and cost-effectiveness for HER-2 positive two plus in IHC. MethodsWe performed a systematic search via PubMed, Scopus, Cochrane Library and Web of Science databases for human diagnostic studies reported the levels of serum HER2 in breast cancer patients, which was confirmed using histopathological examination such as immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Meta-analyses were carried out for sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR) and negative likelihood ratio (NLR). ResultsFourteen studies entered into the study. The meta-analysis indicated that serum HER2 levels had sensitivity 53.05 (95%CI 40.82-65.28), specificity 79.27 (95%CI 73.02-85.51), accuracy 72.06 (95%CI 67.04-77.08), PPV 56.18 (95%CI 44.16-68.20), NPV 76.93 (95%CI 69.56-84.31), PLR 2.10 (95%CI 1.69-2.50) and NLR 0.58 (95%CI 0.44-0.71). ConclusionsOur findings revealed that, although serum HER2 levels showed a low sensitivity for breast cancer diagnosis, its specificity is significantly high in this regard. Hence, it seems that measurement of serum HER2 levels can play a significant role as a verification test for initial negative screening test results, especially in low-income regions due to its cost-effectiveness and ease of implementation in comparison with monitoring of tissue HER-2. Legal entity responsible for the studyAmir Shamshirian and Reza Alizadeh-Navaei. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Evaluation of Human Epidermal Growth Factor Receptor-2 in Iraqi Women with Breast Cancer

Background:Breast cancer (BC) is the most common malignancy in Iraqi women in the recent years. There are many indicated marker for detection BC and determination the development of the tumor stage, one of the most important marker is human epidermal growth factor receptor-2 (HER2). Objective:To evaluation of serum and tissue HER2 levels among BC women and non BC women. Patients and Methods: Preoperative blood samples were collected from breast cancer women. Patients were newly diagnosing and did not receive neither radiotherapy nor chemotherapy treatment preoperatively.For the control, blood sample was collected from non-breast cancer women. All blood samples subjected to determine the serum HER-2 level. Results: A total of 52 patients with breast cancer and 30 of control were included in this study. The result showed increasing significant in serum concentration of HER-2 among BC patient compared to control and tissue her-2 positive BC patient have significantly higher serum concentration of HER-2 compared to BC patients who were tissue her-2 negative (16.23±10.37 ng/ml, 10.33±5.73 ng/ml) respectively. Conclusion: Serum HER-2 level was positively associated with tissue HER-2 level, for that is an important marker for diagnosis and monitoring BC progression.

Polyethylene glycol-conjugated HER2-targeted peptides as a nuclear imaging probe for HER2-overexpressed gastric cancer detection in vivo

BackgroundThe human epidermal growth factor receptor 2 (HER2) involved proliferation, angiogenesis, and reduced apoptosis in gastric cancer (GC), which is a common target for tumor therapy. HER2 is usually overexpressed in more than 15% GC patients, developing a reliable diagnostic tool for tumor HER2 detection is important. In this study, we attend to use polyethylene glycol (PEG) linked anti-HER2/neu peptide (AHNP-PEG) as a nuclear imaging agent probe for HER2 detection in GC xenograft animal model.MethodsThe HER2 expression of human sera and tissues were detected in GC patients and normal subjects. GC cell lines NCI-N87 (high HER2 levels) and MKN45 (low HER2 levels) were treated with AHNP-PEG to assess the cell viability and HER2 binding ability. The NCI-N87 was treated with AHNP-PEG to observe the level and phosphorylation of HER2. The MKN45 and NCI-N87-induced xenograft mice were intravenous injection with fluorescence labeled AHNP-PEG for detecting in vivo fluorescence imaging properties and biodistribution. The AHNP-PEG was conjugated with diethylenetriaminopentaacetic acid (DTPA) for indium-111 labeling (111In-DTPA-AHNP-PEG). The stability of was assessed in vitro. The imaging properties and biodistribution of 111In-DTPA-AHNP-PEG were observed in NCI-N87-induced xenograft mice.ResultsThe serum HER2 (sHER2) levels in GC patients were significantly higher than the normal subjects. The sHER2 levels were correlated with the tumor HER2 levels in different stages of GC patients. The AHNP-PEG inhibited the cell growth and down-regulated HER2 phosphorylation in HER2-overexpressed human GC cells (NCI-N87) via specific HER2 interaction of cell surface. In addition, the GC tumor tissues from HER2-postive xenograft mice presented higher HER2 fluorescence imaging as compared to HER2-negative group. The HER2 levels in the tumor tissues were also higher than other organs in NCI-N87-induced xenograft mice. Finally, we further observed that the 111In-DTPA-AHNP-PEG was significantly enhanced in tumor tissues of NCI-N87-induced xenograft mice compared to control.ConclusionsThese findings suggest that the sHER2 measurement may be as a potential tool for detecting HER2 expressions in GC patients. The radioisotope-labeled AHNP-PEG may be useful to apply in GC patients for HER2 nuclear medicine imaging.

Clinical Relevance of Serum HER2 and Circulating Tumor Cell Detection in Metastatic Breast Cancer Patients.

Presence of circulating tumor cells (CTCs) is associated with impaired survival in metastatic breast cancer (MBC). This study was designed to evaluate whether assessment of serum HER2 (sHER2) levels provide additional prognostic information in MBC. Two hundred and fifty-three MBC patients were enrolled in this multicentre trial. CTCs were detected before the start of first- or later-line treatment using the CellSearch system. sHER2 was determined using ELISA. ≥5 CTCs were detected in 122 of 245 evaluable patients (49.8%). One hundred and nineteen of 251 patients (47%) had sHER2 levels above 15 ng/ml. Median overall survival (OS) was 16.3 months in patients with elevated sHER2; median OS in patients with non-elevated sHER2 has not been reached (p=0.001). Patients with ≥5 CTCs were more likely to present with elevated sHER2 (61% vs. 33% in those with <5 CTC; p<0.001). In patients with HER2-negative tumors, elevated sHER2 was associated with shorter OS and PFS; in HER2-positive patients with OS only. Including sHER2, CTC status and established prognostic factors into a multivariate analysis, only the presence of CTCs and higher-line of therapy remained independent predictors of OS. Elevated levels of sHER2 are associated with worse survival, irrespective of the HER2 status of the tumor. However, sHER2 does not provide additional prognostic information in patients with known CTC status.

Serum HER2 level during chemotherapy as a biomarker for advanced gastric cancer.

29 Background: Recent studies showed that serum HER2 levels correlated with tissue HER2 status in gastric cancer. The aim of this prospective study (UMIN000006442, 000006445) was to investigate changes in serum HER2 levels and tissue HER2 status during chemotherapy for advanced gastric cancer (AGC). Methods: Chemotherapy (Capecitabine and cisplatin) with and without trastuzumab was administered to patients with HER2-positive and HER2-negative AGC, respectively. Serum HER2 level was measured using chemiluminescense immunoassay (CLIA) at 4 points: at the initial diagnosis, after two cycles of chemotherapy, at the initial evaluation of tumor response, and at the time of progression. If possible, second biopsy was performed at progression to compare tissue HER2 status before and after chemotherapy. Results: Thirty-three patients (14 HER2-positive and 19 HER2-negative) with a median age of 67 years (range 51-80) were recruited. The median baseline serum HER2 level of the HER2-positive group was significantly higher than that of the HER2-negative group (p = 0.038, 12.0 ng/ml (range 6.5-148.0) and 8.2 ng/ml (4.5-27.2), respectively). A Decrease in serum HER2 level was correlated with tumor response in the HER2-positive group while it was not in the HER2-negative group. Tissue samples at the time of progression were obtained in 6 out of 19 HER2-negative cases. Of these, serum HER2 level elevated at progression in 4 cases, and tissue HER2 status has turned to positive at tumor progression in one case. In the HER2-positive group, tissue samples at tumor progression were obtained in 2 cases, and both showed HER2-positive result, same as the initial diagnosis. Conclusions: Serum HER2 could be useful as a response indicator in HER2-positive AGC. Tissue HER2 status may change from negative to positive over time and serum HER2 has a possibility to predict it. Further studies are needed to confirm these findings. Clinical trial information: UMIN000006442,000006445.