High-titer HER-2/neu protein-specific antibody can be detected in patients with early-stage breast cancer.

1997 ◽  
Vol 15 (11) ◽  
pp. 3363-3367 ◽  
Author(s):  
M L Disis ◽  
S M Pupa ◽  
J R Gralow ◽  
R Dittadi ◽  
S Menard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Specific Antibody ◽  
Primary Tumor ◽  
Early Stage ◽  
High Titer ◽  
Enzyme Linked Immunosorbent Assay ◽  
Breast Cancer Patients ◽  
Specific Antibodies ◽  
Her 2

PURPOSE To evaluate HER-2/neu-specific antibody immunity in patients with breast cancer, to determine the rate of occurrence of serum antibodies to HER-2/neu in patients with breast cancer, and to relate the presence of specific immunity to overexpression of HER-2/neu protein in primary tumor. METHODS The antibody response to HER-2/neu protein was analyzed in 107 newly diagnosed breast cancer patients. Sera was analyzed for the presence of HER-2/neu-specific antibodies with a capture enzyme-linked immunosorbent assay (ELISA) and verified by Western blot. Sera from 200 volunteer blood donors was used as a control population. RESULTS The presence of antibodies to HER-2/neu correlated with the presence of breast cancer. HER-2/neu antibodies at titers of > or = 1:100 were detected in 12 of 107 (11%) breast cancer patients versus none of 200 (0%) normal controls (P < .01). The presence of antibodies to HER-2/neu also correlated to overexpression of HER-2/neu protein in the patient's primary tumor. Nine of 44 (20%) patients with HER-2/neu-positive tumors had HER-2/neu-specific antibodies, whereas three of 63 (5%) patients with HER-2/neu-negative tumors had antibodies (P = .03). The antibody responses could be substantial. Titers of greater than 1:5,000 were detected in five of 107 (5%). CONCLUSION The presence of HER-2/neu antibodies in breast cancer patients and the correlation with HER-2/neu-positive cancer implies that immunity to HER-2/neu develops as a result of exposure of patients to HER-2/neu protein expressed by their own cancer. These findings should stimulate further studies to develop the detection of immunity to oncogenic proteins as tumor markers, as well as the development and testing of vaccine strategies to induce and augment immunity to HER-2/neu for the treatment of breast cancer or prevention of recurrent disease.

scholarly journals Clinical Significance of ARID1A and ANXA1 in HER-2 Positive Breast Cancer

2020 ◽  
Vol 9 (12) ◽  
pp. 3911
Author(s):  
Rita Silva-Oliveira ◽  
Filipa Ferreira Pereira ◽  
Sara Petronilho ◽  
Ana Teresa Martins ◽  
Ana Lameirinhas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Breast Cancer Mortality ◽  
Inverse Association ◽  
Patient Stratification ◽  
Breast Cancer Patients ◽  
Trastuzumab Resistance ◽  
Luminal B ◽  
Her 2

Background: trastuzumab is considered the standard of care for human epidermal growth factor receptor-2 (HER-2+) breast cancer patients. Regardless of the benefits of its use, many early-stage patients eventually recur, and usually, the disease progresses within a year. Since about half of the HER-2+ patients do not respond to trastuzumab, new biomarkers of prognosis and prediction are warranted to allow a better patient stratification. Annexin A1 (ANXA1) was previously reported to contribute to trastuzumab resistance through AKT activation. An association between adenine thymine-rich interactive domain 1A (ARID1A) loss and ANXA1 upregulation was also previously suggested by others. Methods: in this study, we examined tissue samples from 215 HER-2+ breast cancer patients to investigate the value of ARID1A and ANXA1 protein levels in trastuzumab response prediction and patient outcome. Expression of ARID1A and ANXA1 were assessed by immunohistochemistry. Results: contrary to what was expected, no inverse association was found between ARID1A and ANXA1 expression. HER-2+ (non-luminal) tumours displayed higher ANXA1 expression than luminal B-like (HER-2+) tumours. Concerning trastuzumab resistance, ARID1A and ANXA1 proteins did not demonstrate predictive value as biomarkers. Nevertheless, an association was depicted between ANXA1 expression and breast cancer mortality and relapse. Conclusions: overall, our results suggest that ANXA1 may be a useful prognostic marker in HER-2+ patients. Additionally, its ability to discriminate between HER-2+ (non-luminal) and luminal B-like (HER-2+) patients might assist in patient stratification regarding treatment strategy.

Serial monitoring for circulating cancer cells in blood samples of stage 1–4 breast cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 623-623
Author(s):  
K. H. Tkaczuk ◽  
N. S. Tait ◽  
K. Chua ◽  
F. Feldman ◽  
S. A. Lesko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Primary Tumor ◽  
Receptor Expression ◽  
Breast Cancer Patients ◽  
Blood Samples ◽  
Circulating Cancer Cells ◽  
Her 2 ◽  
Stage 1

623 Serial monitoring for presence, number & characterization of circulating cancer cells (CCC) may provide valuable information that may be relevant to prognosis and treatment outcomes of breast cancer patients (BCP). We conducted a serial blood sampling study at the University of Maryland in BCP with stage 1–4 breast carcinoma. 15–20 ml of venous blood were collected before the start of systemic therapy and periodically thereafter & processed using negative selection method with double-gradient centrifugation & magnetic cell sorting to remove WBCs. Digital images of FITC-positive epithelial cells were acquired with a fluorescence microscope & counted. CCC from 41 patients (Pts) were also stained with Trastuzu-mAb-532 to quantify the HER-2/neu cell surface receptor expression relative to a fluorescence standard. 105 Pts were accrued & 415 blood samples tested (median number of samples/pt; 4 (1–8). During the 24 mos. monitoring period CCC were detected in 57 of 105 pts (54%). The Table below shows that presence of >10 CCC/sample is associated with decreased survival and increased probability of having metastatic disease.(Exact chi-square test for presence vs. absence of metastatses in A, B, C, D groups, P < 0.0001; Fisher’s exact test to compare individual groups: for B vs C+ D, P < 0.001; B vs C, P=0.001). HER-2/neu expression was assessed in CCC of 25 pts (minimum of 4 CCC per sample) as compared with strongly HER-2/neu positive control cell line SKBR-3. 10 Pts were positive & 15 negative for HER-2/neu over-expression in CCC. CCC data & primary tumor data concurred in 6 of 7 Her-2/neu primary tumor tissue positive Pts & in 12 of 13 Her-2/neu primary tissue negative Pts. For 5 Pts tissue data was not available. Conclusions: Increasing CCC numbers/sample appear to correlate with adverse outcome of BCP. Our CCC Test may provide valuable information about prognosis of stage 1–4 BCP. HER-2/neu expression could be quantified in individual CCC & concurred with primary tumor data in 90% of Pts. Supported by NCI Grant CA081903 [Table: see text] [Table: see text]

scholarly journals Whole Genome Sequencing in single CTC improves clinical outcome in Her-2 negative breast cancer patients

2020 ◽  
Author(s):  
Bo Yu ◽  
Yongping Li ◽  
Hao Yuan ◽  
Bin Zhang ◽  
Xiaofei Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Genome Sequencing ◽  
Primary Tumor ◽  
Tumor Tissue ◽  
Whole Genome ◽  
Breast Cancer Patients ◽  
Her2 Gene ◽  
Her 2

Abstract Background Tumor tissues are usually highly heterogeneous and difficult to characterize which could mislead treatment strategy. Circulating tumor cells (CTCs) represent the most active and invasive tumor cells. This study explored the feasibility of individualized treatment of breast cancer patients based on genome sequencing of single cell CTC. Methods Twenty-four CTCs were identified in three patients with breast cancer. For each patient, one polyploid CTC was captured and on which the whole genome sequencing (WGS) was performed. Based on the histopathological Her-2 status in tumor tissue and the HER2 gene status in WGS results of CTC, we adjusted treatment strategies, and monitored disease progression. Results Patient ID1 and ID2 are Her-2 positive in both primary tumor and HER2 abnormal in the DNA of CTC. In patient ID3, histological examination of primary tumor and liver metastases revealed Her-2 negative, but the WGS analysis of CTC showed that the HER2 gene was amplified and mutated. After adjusting treatment according to the results of CTC sequencing, the liver metastases and pleural effusion were significantly reduced, CTC number and ctDNA burden were decreased. In addition, some potential therapeutic targets and mutations in drug-resistant genes were found. Conclusion The results of CTC sequencing effectively guided treatment of a patient with HER2 gene amplification/mutation in CTC but with Her-2 negative on tumor tissue. CTC sequencing is useful in resolving the heterogeneity of tumors and providing precision medicine for patients.

scholarly journals Detection of Genomically Aberrant Cells within Circulating Tumor Microemboli (CTMs) Isolated from Early-Stage Breast Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1409
Author(s):  
Marco Silvestri ◽  
Carolina Reduzzi ◽  
Giancarlo Feliciello ◽  
Marta Vismara ◽  
Thomas Schamberger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Primary Tumor ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Associated Functions ◽  
Circulating Tumor Microemboli

Circulating tumor microemboli (CTMs) are clusters of cancer cells detached from solid tumors, whose study can reveal mechanisms underlying metastatization. As they frequently comprise unknown fractions of leukocytes, the analysis of copy number alterations (CNAs) is challenging. To address this, we titrated known numbers of leukocytes into cancer cells (MDA-MB-453 and MDA-MB-36, displaying high and low DNA content, respectively) generating tumor fractions from 0–100%. After low-pass sequencing, ichorCNA was identified as the best algorithm to build a linear mixed regression model for tumor fraction (TF) prediction. We then isolated 53 CTMs from blood samples of six early-stage breast cancer patients and predicted the TF of all clusters. We found that all clusters harbor cancer cells between 8 and 48%. Furthermore, by comparing the identified CNAs of CTMs with their matched primary tumors, we noted that only 31–71% of aberrations were shared. Surprisingly, CTM-private alterations were abundant (30–63%), whereas primary tumor-private alterations were rare (4–12%). This either indicates that CTMs are disseminated from further progressed regions of the primary tumor or stem from cancer cells already colonizing distant sites. In both cases, CTM-private mutations may inform us about specific metastasis-associated functions of involved genes that should be explored in follow-up and mechanistic studies.

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