scholarly journals Detection of HER2-status and genomic analysis of disseminated cancer cells (DCCs) of non-metastatic breast cancer patients with HER2-negative and positive primary tumors

2015 ◽  
Vol 26 ◽  
pp. iii10
Author(s):  
E. Doblinger ◽  
O. Schmidt ◽  
Z. Czyz ◽  
G. Haunschild ◽  
B. Rack ◽  
...  
2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21029-e21029
Author(s):  
Christopher Neal ◽  
Sujita Sukumaran ◽  
Vishal Gupta ◽  
Insiya Jafferji ◽  
Dave Hasegawa ◽  
...  

e21029 Background: Up-regulation of epithelial mesenchymal transition (EMT) and the reduction of epithelial marker expression is associated with invasion, cancer progression, resistance to conventional therapies and poor prognosis. ApoStream, a novel continuous flow dielectrophoresis field-flow fractionation (DEP-FFF) device, was used to enable antibody-independent capture of circulating cancer cells (CCCs,also referred to as circulating tumor cells, CTC) for subsequent phenotyping of EMT markers. Methods: A side-by-side comparison of CellSearch and ApoStream was performed on 10 metastatic breast cancer patients. A multiplexed immunofluorescent assay and laser scanning cytometry analyses were used to unambiguously identify CK+/CD45–/DAPI+ CCCs and quantify their EpCAM and vimentin expression. Results: ApoStream recovered CK+/CD45–/DAPI+ CCCs from each breast cancer patient sample tested (mean=255 CCCs per 7.5 ml blood, see Table). ApoStream consistently recovered significantly higher number of CCCs compared to CellSearch (p=0.024). ApoStream recovered both EpCAM+ and EpCAM– CCCs in 50% and 90% of patients, respectively. Vimentin+ CCCs were isolated from 90% of patients. Conclusions: ApoStream’s higher capture efficiency demonstrated the majority of CCCs from breast cancer patients were EpCAM negative and vimentin-positive. ApoStream technology can be used to monitor CCCs undergoing EMT. [Table: see text]


2020 ◽  
Vol 38 (29_suppl) ◽  
pp. 282-282
Author(s):  
Sandhya Mehta ◽  
Jinlin Song ◽  
Melissa Pavilack ◽  
Jipan Xie ◽  
Xiaoyu Nie ◽  
...  

282 Background: HER2-positive (+) metastatic breast cancer (mBC) has a poor prognosis and many patients require multiple lines of HER2 targeted regimens. This study aims to examine the treatment sequencing of anti-HER2 regimens for HER2+ mBC among Medicare beneficiaries. Methods: A retrospective study was conducted using linked 1999-2016 Surveillance, Epidemiology, and End Results (SEER) cancer registries and Medicare claims. Adults patients who had mBC diagnosis, HER2+ status documented in SEER or claims of ≥1 anti-HER2 drug, continuous enrollment in Medicare from the date of mBC diagnosis until end of study period/death, and 2 anti-HER2 regimens with or without chemotherapy (Ch) or hormonal therapy (HT) were included. Discontinuation of anti-HER2 regimen was defined as the absence of claims for all anti-HER2 drugs for >60 days, or initiation of a different anti-HER2 drug. Re-initiation of the same regimen after >60 days was considered as a new regimen. The first two anti-HER2 regimens and subsequent therapies were summarized. Results: 804 patients with 2 anti-HER2 regimens were included. Trastuzumab (T) based regimen (defined as: T±Ch/HT; without other anti-HER2 drugs) was the most common 1st regimen (82%), followed by T+ pertuzumab (P) (14%) and lapatinib (L) (3%). For the 2nd regimen, T (52%) was most common, followed by T+P (18%), L (11%), trastuzumab emtansine (T-DM1) (11%) and T+L (7%). After a 2nd regimen, 578 (72%) initiated a subsequent therapy, with over half switching to non-targeted therapies [52%; HT alone (35%), Ch±HT (17%)] followed by T (17%), T-DM1 (12%) and T+P (7%). Among those with subsequent therapy, 2 T-based regimens followed by HT alone (21%) was the most common sequence. After the 1st regimen, 52% patients reused the same anti-HER2 drugs in the 2nd regimen, 21% added another anti-HER2 drug and 27% switched to a different anti-HER2 regimen. After the 2nd regimen, 14% reused anti-HER2 drugs and 6% added another anti-HER2 drug, 25% switched to a different anti-HER2 regimen; 15% reused anti-HER2 drugs from the 1st regimen. Conclusions: Trastuzumab based regimen was the mainstay of anti-HER2 drug regimens during the study timeframe. Despite availability of multiple anti-HER2 drugs, reuse of prior anti-HER2 drugs and switching to non-targeted therapies alone were common after using 2 anti-HER2 regimens. These findings underscore the unmet needs in later lines of therapy. Recently approved anti-HER2 agents may provide additional treatment options for pre-treated HER2+ metastatic breast cancer patients.


2020 ◽  
Author(s):  
Shahan Mamoor

Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published microarray and gene expression data (3, 4) to discover in an unbiased manner the most striking transcriptional features of trastuzumab treatment. We identified the cytokine interleukin-6 (IL-6) (5) as among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab. The primary tumors of breast cancer patients treated with trastuzumab expressed higher levels of IL-6 messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of IL-6 in primary tumors of the breast, suggesting that increased primary tumor expression of IL-6 in the primary tumors of patients with breast cancer, a cytokine whose serum levels are correlated with worse patient survival outcomes in metastatic breast cancer (6), is a direct transcriptional result of treatment with trastuzumab.


2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 174-174
Author(s):  
S. Y. Jung ◽  
M. Q. Rosenzweig ◽  
S. M. Sereika ◽  
F. Linkov ◽  
A. Brufsky ◽  
...  

174 Background: It is generally accepted that patients with breast cancer metastases have poor survival. Metastatic breast cancer patients can be considered a heterogeneous population with a varied clinical course, which underscores the need for accurate prediction of survival based on prognostic factors. The purpose of the present study was to identify factors related to survival in breast cancer patients after diagnosis with metastatic disease. Methods: A total of 557 patients with breast cancer metastasis diagnosis seen at one large urban practice have been followed up between January 1, 1999 and June 30, 2008. Demographic, tumor characteristics, clinical factors as predictors of survival were analyzed using Cox regression model. Results: The median survival length was 40 months (range 1-114 months) with 269 (48.3%) alive and 288 (51.7%) dead. This study demonstrated that hypertension, estrogen receptor (ER) and/or progesterone receptor (PR) status, human epidermal growth factor receptor-2 (HER2) status, number of metastatic sites, and body mass index (BMI) at diagnosis with metastatic breast cancer were the most relevant prognostic factors for survival after metastasis. Conclusions: Findings of this study may form a foundation for the corpus of knowledge explaining the outcome differences in treatment of patients with metastatic breast cancer, potentially helping to create tailored counseling and personalized treatment approaches for this vulnerable group. [Table: see text]


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 858
Author(s):  
Jagyeong Oh ◽  
Davide Pradella ◽  
Changwei Shao ◽  
Hairi Li ◽  
Namjeong Choi ◽  
...  

Aberrant alternative splicing (AS) is a hallmark of cancer and a potential target for novel anti-cancer therapeutics. Breast cancer-associated AS events are known to be linked to disease progression, metastasis, and survival of breast cancer patients. To identify altered AS programs occurring in metastatic breast cancer, we perform a global analysis of AS events by using RNA-mediated oligonucleotide annealing, selection, and ligation coupled with next-generation sequencing (RASL-seq). We demonstrate that, relative to low-metastatic, high-metastatic breast cancer cells show different AS choices in genes related to cancer progression. Supporting a global reshape of cancer-related splicing profiles in metastatic breast cancer we found an enrichment of RNA-binding motifs recognized by several splicing regulators, which have aberrant expression levels or activity during breast cancer progression, including SRSF1. Among SRSF1-regulated targets we found DCUN1D5, a gene for which skipping of exon 4 in its pre-mRNA introduces a premature termination codon (PTC), thus generating an unstable transcript degraded by nonsense-mediated mRNA decay (NMD). Significantly, distinct breast cancer subtypes show different DCUN1D5 isoform ratios with metastatic breast cancer expressing the highest level of the NMD-insensitive DCUN1D5 mRNA, thus showing high DCUN1D5 expression levels, which are ultimately associated with poor overall and relapse-free survival in breast cancer patients. Collectively, our results reveal global AS features of metastatic breast tumors, which open new possibilities for the treatment of these aggressive tumor types.


Author(s):  
Baojuan Han ◽  
Lina Dong ◽  
Jing Zhou ◽  
Yan Yang ◽  
Jiaxun Guo ◽  
...  

AbstractThis work investigated the clinical prognostic implications and biological function of plasma soluble programmed cell death ligand 1 in breast cancer patients. Plasma sPD-L1 levels of recurrent/metastatic breast cancer patients were determined, and the association of sPD-L1 levels and metastatic progression-free survival and metastatic overall survival was assessed. The PD-L1 expression on breast cancer cells was analyzed by flow cytometry, and the level of sPD-L1 in the supernatant of breast cancer cells was determined by enzyme-linked immunosorbent assay. Furthermore, the effect of sPD-L1 on the proliferation and apoptosis of T lymphocytes was detected by WST-1 assay and flow cytometry. The plasma sPD-L1 levels in 208 patients with recurrent/metastatic breast cancer before receiving first-line rescue therapy were measured. The optimal cutoff value of plasma sPD-L1 for predicting disease progression was 8.774 ng/ml. Univariate and multivariate analyses identified high sPD-L1 level (≥ 8.774 ng/ml) and visceral metastasis were independent factors associated with poor prognosis. Relevance analysis showed that the plasma sPD-L1 level was weaklyassociated with some systemic inflammation markers, including white cell count (WBC), absolute monocytecount, and absolute neutrophil count. Furthermore, we found sPD-L1 could be found in supernatant of culture with breast cancer cell line expressing PD-L1 on the cell surface and inhibit T lymphocyte function, playing a negative regulatory role in cellular immunity. sPD-L1 was a good tumor predictive maker in breast cancer and it may play a potentially important role in immune tolerance.


Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5876
Author(s):  
Konstantinos S. Papadakos ◽  
Catharina Hagerling ◽  
Lisa Rydén ◽  
Anna-Maria Larsson ◽  
Anna M. Blom

Cartilage oligomeric matrix protein (COMP) is a regulator of the extracellular matrix and is expressed primarily in the cartilage. Recently, COMP expression was also documented in breast cancer patients both in sera and tumor biopsies, in both of which it could serve as an independent prognostic marker. This study aimed to assess COMP as a potential biomarker in the group of metastatic breast cancer patients. Levels of COMP were measured by ELISA in serum samples of 141 metastatic breast cancer patients. Biopsies from primary tumors, synchronous lymph node metastases, and distant metastases were stained for COMP expression. The levels of serum COMP were higher in patients with ER- and HER2-positive tumors when compared to triple-negative tumors and correlated with the presence of bone and lung metastases, circulating tumor cell count, and clusters. Most of the primary tumors expressing COMP (70%) retained the expression also in the lymph node metastases, which correlated with visceral metastases and reduced survival. In conclusion, COMP appears as a valuable biomarker in metastatic breast cancer patients indicating a more severe stage of the disease. Serum COMP levels were associated with specific types of metastases in patients with metastatic breast cancer emphasizing that further studies are warranted to elucidate its potential role as a monitoring marker.


2011 ◽  
Vol 17 (11) ◽  
pp. 3600-3618 ◽  
Author(s):  
Anieta M. Sieuwerts ◽  
Bianca Mostert ◽  
Joan Bolt-de Vries ◽  
Dieter Peeters ◽  
Felix E. de Jongh ◽  
...  

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