scholarly journals HER2 Phenotyping of CTCs By Peptide-Functionalized Nanoparticles As The Diagnostic Biomarkers of Anti-HER2 Treatment in Breast Cancer

2021 ◽  
Author(s):  
Mengting Wang ◽  
Yaxin Liu ◽  
Bin Shao ◽  
Xiaoran Liu ◽  
Chen Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Combination Therapy ◽  
Dynamic Change ◽  
Progression Free Survival ◽  
Chemotherapeutic Agents ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Breast Cancer Patients ◽  
Efficient Detection ◽  
High Efficient

Abstract Background: The efficacy of anti-human epidermal growth factor receptor 2 (HER2/neu) treatment is impacted by tissue-based evaluation bias due to tumor heterogeneity and dynamic changes of HER2 in breast cancer. Circulating tumor cell (CTC)-based HER2 phenotyping provides an integral and real-time assessment, benefiting accurate HER2 diagnosis for improved therapeutics.Methods: The study was exploratory. Fifty-four breast cancer patients, including 26 histopathologic HER2/neu-positive (Histo-HER2/neu+) and 28 HER2/neu-negative (Histo-HER2/neu+), were enrolled for blood draws before a new line of treatment. We used peptide-functionalized magnetic nanoparticles to isolate CTCs from 2.0 mL whole blood and determined HER2 phenotypes of the enriched CTCs by immunocytochemistry (ICC). We investigated the correlation of the enumeration and HER2 phenotyping on baseline CTCs with the diagnosis, the prognosis, and the efficacy of the trastuzumab in combination with chemotherapeutic agents of breast cancer. We also explored the dynamic change of HER2 phenotypes on CTCs after the combination therapy in a cohort of Histo-HER2/neu+ individuals (n = 14).Results: We achieved high-efficient detection of the CTC-positive cases (≥ 3 CTCs) (38/54, 70.4%), from whom 71.1% (27/38) had a concordant HER2 status on CTCs and tumor tissues at baseline. Pretheraputic CTC enumeration showed a significant correlation with the histopathologic diagnosis (e.g. estrogen receptor/progesterone receptor (ER/PR) status or proliferation of cancer cells) and the progression-free survival/overall survival (PFS/OS) of breast cancer. However, it was not a practicable biomarker to predict the efficacy of the trastuzumab-based combination therapy. In contrast, we demonstrated a significantly higher possibility of good overall responses in the patients with < 3 CTCs (P = 0.006) or with HER2 overexpression in CTCs (CTC-HER2+) at baseline, as compared to the individuals without HER2 overexpression in CTCs (CTC-HER2–) (P = 0.028).Conclusions: We demonstrate the significance of the peptide-functionalized magnetic nanoparticle in noninvasive detection and HER2 phenotyping of CTCs, and highlight its diagnostic and prognostic values for the patients about to start the anti-HER2 treatment.

HER2 expression and efficacy of preoperative paclitaxel and 5-fluorouracil, cyclophosphamide, doxorubicin chemotherapy in breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 548-548
Author(s):  
L. Pusztai ◽  
F. Andre ◽  
C. Mazouni ◽  
C. Liedtke ◽  
S. Kau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Survival Rates ◽  
Pathologic Complete Response ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Her2 Expression ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer ◽  
Tau Expression

548 Purpose: We examined the correlation between HER2 expression and pathologic complete response (pCR) to paclitaxel/FAC (T/FAC) preoperative chemotherapy in stage II-III breast cancer. Patients and Methods: Retrospective analysis of data including 534 patients treated with preoperative T/FAC was performed. Gene expression results were available from a subset of 132 patients and were used to examine the co-expression of HER2 and topoisomerase II a (TOP2A) and microtubule associated protein tau (MAP-Tau). Results: Of the 534 patients, 105 (20%) had HER2 overexpressing (HER2+) breast cancer. The pCR rates were 33% and 15% for patients with HER2+ and HER2- tumors (P<0.001). The 5-year relapse-free survival rates were 94% and 70% in HER2+ tumors with and without pCR (P=0.009). In multivariate analysis ER-negative status (OR 3.1, 95% CI 1.7–5.5, P < 0.001), high nuclear grade (OR 6.7, 95% CI 3.1–14.2, P < 0.001), weekly paclitaxel regimen (OR 2.6, 95% CI 1.5–4.5, P <0.001), and HER2 overexpression (OR 2.4, 95% CI 1.3–4.2, P = 0.003) were significant predictors of pCR. Among ER- cancers, the pCR rates were 50% (95%CI: 36–64%) in HER2+ (n=24/48) and 30% (95%CI: 23–37%) in HER2- disease (n=48/159), P = 0.02. Among ER+ cancers, the pCR rate was 19% (95% CI: 9–29%) in HER2+ (n=11/57) and 6% (95% CI: 3–9%) in HER2- disease (n=17/270), P = 0.003. In the gene expression data, HER2 overexpression was associated with lower expression of MAP-tau (mean 303 vs 500, p=0.001) and higher expression of TOP2A mRNAs (mean 398 vs 274, p=0.048) in patients with ER+ disease. All ER- cancers had low MAP-Tau expression (compared to ER+ cancers) regardless of HER2 status. Conclusion: HER2 overexpression is associated with higher rate of pCR to preoperative T/FAC chemotherapy in both ER- and ER+ cancers. HER2 overexpression correlates with increased TOP2A and decreased MAP-Tau expression in ER+ cancers which could explain increased anthracycline and taxane sensitivity of these tumors. No significant financial relationships to disclose.

scholarly journals High Galectin-7 and Low Galectin-8 Expression and the Combination of both are Negative Prognosticators for Breast Cancer Patients

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 953
Author(s):  
Anna Trebo ◽  
Nina Ditsch ◽  
Christina Kuhn ◽  
Helene Hildegard Heidegger ◽  
Christine Zeder-Goess ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cell ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Her2 Status ◽  
Cancer Tissue ◽  
Breast Cancer Patients ◽  
Patient Age ◽  
Free Survival ◽  
Patient Âgé

Galectins are commonly overexpressed in cancer cells and their expression pattern is often associated with the aggressiveness and metastatic phenotype of the tumor. This study investigates the prognostic influence of the expression of galectin-7 (Gal-7) and galectin-8 (Gal-8) in tumor cell cytoplasm, nucleus and on surrounding immune cells. Primary breast cancer tissue of 235 patients was analyzed for the expression of Gal-7 and Gal-8 and correlated with clinical and pathological data and the outcome. To identify immune cell subpopulations, immunofluorescence double staining was performed. Significant correlations of Gal-7 expression in the cytoplasm with HER2-status, PR status, patient age and grading, and of Gal-8 expression in the cytoplasm with HER2-status and patient age and of both galectins between each other were found. A high Gal-7 expression in the cytoplasm was a significant independent prognosticator for an impaired progression free survival (PFS) (p = 0.017) and distant disease-free survival (DDFS) (p = 0.030). Gal-7 was also expressed by tumor-infiltrating macrophages. High Gal-8 expression in the cytoplasm was associated with a significantly improved overall survival (OS) (p = 0.032). Clinical outcome in patients showing both high Gal-7 and with low Gal-8 expression was very poor. Further understanding of the role of galectins in the regulation and interaction of tumor cells and macrophages is essential for finding new therapeutic targets.

LINAC-based stereotactic radiosurgery/radiotherapy for brain metastases in patients with breast cancer

2021 ◽  
pp. 1-9
Author(s):  
Ankita Gupta ◽  
Budhi Singh Yadav ◽  
Nagarjun Ballari ◽  
Namrata Das ◽  
Ngangom Robert
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Progression Free Survival ◽  
Rank Test ◽  
Karnofsky Performance Score ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Prior Surgery

Abstract Background: Brain metastases (BM) are common in patients with HER2-positive and triple-negative breast cancer. In this study we aim to report clinical outcomes with LINAC-based stereotactic radiosurgery/radiotherapy (SRS/SRT) for BM in patients of breast cancer. Methods: Clinical and dosimetric records of breast cancer patients treated for BM at our institute between May, 2015 and December, 2019 were retrospectively reviewed. Patients of previously treated or newly diagnosed breast cancer with at least a radiological diagnosis of BM; 1–4 in number, ≤3·5 cm in maximum dimension, with a Karnofsky Performance Score of ≥60 were taken up for treatment with SRS. SRT was generally considered if a tumour was >3·5 cm in diameter, near a critical or eloquent structure, or if the proximity of moderately sized tumours would lead to dose bridging in a single-fraction SRS plan. The median prescribed SRS dose was 15 Gy (range 7–24 Gy) and SRT dose was 27 Gy in 3 fractions. Clinical assessment and MR imaging was done at 6 weeks post-SRS and then every 3 months thereafter. Intracranial progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method and subgroups were compared using log rank test. Results: Total, 40 tumours were treated in 31 patients. The median tumour diameter was 2·3 cm (range 1·0–4·6 cm). SRS and SRT were delivered in 27 and 4 patients, respectively. SRS/SRT was given as a boost to whole brain radiotherapy (WBRT) in four patients and as salvage for progression after WBRT in six patients. In general, nine patients underwent prior surgery. The median follow-up was 7·9 months (0·2–34 months). Twenty (64·5%) patients developed local recurrence, 10 (32·3%) patients developed distant intracranial relapse and 7 patients had both local and distant intracranial relapse. The estimated local control at 6 months and 1 year was 48 and 35%, respectively. Median intracranial progression free survival (PFS) was 3·73 months (range 0·2–25 months). Median intracranial PFS was 3·02 months in patients who received SRS alone or as boost after WBRT, while it was 4·27 months in those who received SRS as salvage after WBRT (p = 0·793). No difference in intracranial PFS was observed with or without prior surgery (p = 0·410). Median overall survival (OS) was 21·7 months (range 0·2–34 months) for the entire cohort. Patients who received prior WBRT had a poor OS (13·31 months) as compared to SRS alone (21·4 months; p = 0·699). Conclusion: In patients with BM after breast cancer SRS alone, WBRT + SRS and surgery + SRS had comparable PFS and OS.

scholarly journals Do early HER2-overexpression breast cancer patients benefit from undergoing neoadjuvant trastuzumab and mastectomy? A meta-analysis

2019 ◽  
Vol Volume 11 ◽  
pp. 8043-8054 ◽  
Author(s):  
Lin He ◽  
Qian Wu ◽  
Jing Xiong ◽  
Zhumin Su ◽  
Biyuan Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Her2 Overexpression ◽  
Breast Cancer Patients

scholarly journals VWCE as a potential biomarker associated with immune infiltrates in breast cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qin Huo ◽  
Zhenwei Li ◽  
Siqi Chen ◽  
Juan Wang ◽  
Jiaying Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cell ◽  
Her2 Status ◽  
Cancer Tissue ◽  
M2 Macrophage ◽  
Breast Cancer Patients ◽  
Immune Infiltration ◽  
Potential Biomarker ◽  
Significant Difference ◽  
Factor C

Abstract Purpose Von Willebrand Factor C and EGF Domains (VWCE) is an important gene that regulates cell adhesion, migration, and interaction. However, the correlation between VWCE expression and immune infiltrating in breast cancer remain unclear. In this study, we investigated the correlation between VWCE expression and immune infiltration levels in breast cancer. Methods The expression of VWCE was analyzed by the tumor immune estimation resource (TIMER) and DriverDB databases. Furthermore, genes co-expressed with VWCE and gene ontology (GO) enrichment analysis were investigated by the STRING and Enrichr web servers. Also, we performed the single nucleotide variation (SNV), copy number variation (CNV), and pathway activity analysis through GSCALite. Subsequently, the relationship between VWCE expression and tumor immunity was analyzed by TIMER and TISIDB databases, and further verified the results using Quantitative Real-Time PCR (RT-PCR), Western blotting, and immunohistochemistry. Results The results showed that the expression of VWCE mRNA in breast cancer tissue was significantly lower than that in normal tissues. We found that the expression level of VWCE was associated with subtypes, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status of breast cancer patients, but there was no significant difference in the expression of VWCE was found in age and nodal status. Further analyses indicated that VWCE was correlated with the activation or inhibition of multiple oncogenic pathways. Additionally, VWCE expression was negatively correlated with the expression of STAT1 (Th1 marker, r = − 0.12, p = 6e−05), but positively correlated with the expression of MS4A4A (r = 0.28, p = 0). These results suggested that the expression of VWCE was correlated with immune infiltration levels of Th1 and M2 macrophage in breast cancer. Conclusions In our study, VWCE expression was associated with a better prognosis and was immune infiltration in breast cancer. These findings demonstrate that VWCE is a potential prognostic biomarker and correlated with tumor immune cell infiltration, and maybe a promising therapeutic target in breast cancer.

Buparlisib in Kombination mit Tamoxifen: Rationale für zielgerichtete Therapie bei PIK3CA-mutiertem metastasierten Mammakarzinom bestätigt

2021 ◽  
pp. 1-3
Author(s):  
Carlota Claussen ◽  
Maggie Banys-Paluchowski
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Pik3ca Mutation ◽  
Progression Free Survival ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Open Label ◽  
Pik3ca Mutations ◽  
Hormone Receptor Positive ◽  
Pi3k Inhibition

The PIKTAM study evaluated the efficacy and safety of the PI3K inhibitor buparlisib in combination with tamoxifen in hormone receptor-positive (HR+), HER2-negative advanced breast cancer patients after failure of prior endocrine therapy. In this open-label, single-arm phase II trial, 25 patients were enrolled in 11 sites in Germany. Patients were stratified according to PIK3CA mutation status (tissue and cfDNA from serum samples) and/or loss of PTEN expression. Patients received buparlisib (100mg) and tamoxifen (20mg) once daily on a continuous schedule (28-day cycle) until progression or unacceptable toxicity. Primary endpoint was overall 6-month progression-free survival (PFS) rate. Key secondary endpoints included the 6-month PFS rate in subpopulations, PFS, overall survival, overall response rate (ORR), disease control rate (DCR), and safety. Overall, the 6-month PFS rate was 33.3% (n/N = 7/21, one-sided 95% CI 16.8–100) and median PFS was 6.1 (CI 2.6–10.6) months. The ORR and DCR were 12.5% and 44%. The PIK3CA-mutated subgroup consistently showed the highest 6-month PFS rate (62.5%, n/N = 5/8), median PFS (8.7 months), ORR (40%), and DCR (80%). No new safety signals emerged. Most common adverse events were gastrointestinal disorders (56%), psychiatric/mood disorders (48%), skin rash/hypersensitivity (44%), cardiovascular (40%), and hepatic (32%) events. The trial was prematurely terminated due to the substantially altered risk – benefit profile of buparlisib. Nevertheless, PIK3CA mutations emerged as a clinically feasible and useful biomarker for combined PI3K inhibition and endocrine therapy in patients with HR+ breast cancer. Further biomarker – stratified studies with isoform – specific PI3K inhibitors are warranted. EudraCT No: 2014–000599–24.

scholarly journals Salivary expression of soluble HER2 in breast cancer patients with positive and negative HER2 status

2014 ◽  
pp. 1285 ◽  
Author(s):  
Fatna Laidi ◽  
Amal BOUZIANE ◽  
Amina Lakhdar ◽  
Fatima Zaoui ◽  
Samira Khabouze ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Her2 Status ◽  
Breast Cancer Patients

scholarly journals Concordance Between ER, PR, HER2 neu Receptors Before and After Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Heba F. Taha ◽  
Ola M. Elfarargy ◽  
Reham A. Salem ◽  
Doaa Mandour ◽  
Amira A. Salem ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Her2 Status ◽  
Breast Cancer Patients ◽  
Before And After ◽  
Tumor Phenotype

Abstract Background Introducing neoadjuvant chemotherapy (NCT) in a breast cancer patient may be associated with changes in estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth hormone receptor 2 (HER2) status. Method In our prospective cohort study, we evaluated the impact of change in estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth hormone receptor 2 (HER2) on the prognosis of breast cancer patients treated with neoadjuvant chemotherapy (NCT). We investigated 110 patients with locally advanced breast cancer for ER, PR and HER2 status of their lesions before and after NCT. Result For hormone receptor status (HR) (which include ER, PR) of the residual tumor of the patients after receiving NCT, 12 (10.9%) of them changed from HR (+) to HR (−) and 15 (13.6%) changed from HR (−) to HR (+). For HER2 status after NCT, 8 (7.3%) patients changed from HER2 (+) to HER2 (−) and 9 (8.2%) patients changed from HER2 (−) to HER2 (+). Triple negative (TN) tumor phenotype changes occurred in 17 (15.5%) patients. Patients for whom the HR status changed from positive to negative had poor prognosis for both disease-free survival (DFS) and overall survival (OS) in univariate survival analysis. Conclusion Changes in ER, PR, HER2 status and tumor phenotype in breast cancer patients after NCT had a negative prognostic impact and were associated with a poor prognosis.

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