Cytokeratin-19 (CK19) and mammaglobin (MGB1) gene expression in circulating tumor cells (CTCs) from metastatic breast cancer patients enrolled in the NCCTG trials, N0436 and N0437

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11095-11095
Author(s):  
M. M. Reinholz ◽  
K. A. Kitzmann ◽  
T. J. Hobday ◽  
D. W. Northfelt ◽  
B. LaPlant ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Metastatic Breast Cancer ◽  
Treatment Response ◽  
Cox Regression ◽  
Imaging System ◽  
Metastatic Breast ◽  
Cytokeratin 19 ◽  
Mrna Levels ◽  
Ck19 Mrna

11095 Background: Biologic characterization of CTCs is increasingly important in determining metastatic breast cancer (MBC) patient (pt) prognosis and treatment prediction. Combined preliminary results from two earlier metastatic BC NCCTG trials, N0234 & N0336, suggested that the change in CTC mammaglobin (MGB1) gene expression between baseline and two cycles of chemotherapy predicted tumor response (p=0.04). The objectives of this study were to 1) determine CTC gene expression of CK19 and MGB1 before, during, and after treatment in N0436 & N0437 and 2) determine associations between baseline and post-treatment gene expression and treatment response. Methods: CTCs were enriched using CD45-depletion from ∼10ml EDTA blood obtained from metastatic BC pts before, after two cycles, and at end of treatment with either first/second-line irinotecan plus cetuximab (N0436) or first-line paclitaxel poliglumex and capecitabine (N0437). CK19 and MGB1 mRNA levels were determined using quantitative RT-PCR in baseline and serial CTC samples of up to 19 pts from N0436 and 40 pts from N0437. The relative gene expressions were normalized to β2-microglobulin and calibrated to healthy blood using the 2-ΔΔCt algorithm; a value of 2 was defined as positive for the respective marker. Results: CK19+ mRNA was detected in 58% of baseline samples from N0436 (11/19) and N0437 (23/40). MGB1+ mRNA was detected in 32% (6/19) and 38% (15/40) of N0436 and N0437 baseline samples, respectively. CK19+ mRNA was detected in 50% (7/14) and 56% (29/52) of N0436 and N0437 serial CTC samples, respectively. MGB1+ mRNA was detected in 29% (4/14) and 27% (14/52) of N0436 and N0437 serial CTC samples, respectively. Of the 66 serial samples, 27% of samples (18/66) had turned positive from baseline for CK19 or MGB1. CK19 mRNA was detected in 85% (33/39) of MGB1+ mRNA samples but their baseline mRNA levels were not correlated. Conclusions: CK19 mRNA was detected in MBC pts with similar frequencies to the CellSearch imaging system. CK19 was detected at a higher frequency than MGB1. In the majority of cases, MGB1 was co-expressed with CK19. Associations between gene expression and treatment response using Chi-Squared analyses and Cox regression models will be presented. No significant financial relationships to disclose.

scholarly journals BRMS1 gene expression may be associated with clinico-pathological features of breast cancer

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Li-Zhong Lin ◽  
Miao-Guo Cai ◽  
Yue-Chu Dai ◽  
Zhi-Bao Zheng ◽  
Fang-Fang Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Metastatic Breast Cancer ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Breast Cancer Tissue ◽  
Metastasis Suppressor ◽  
Cancer Tissue ◽  
Mrna Levels ◽  
Pathological Features

Our aim is to investigate whether or not the breast cancer metastasis suppressor 1 (BRMS1) gene expression is directly linked to clinico-pathological features of breast cancer. Following a stringent inclusion and exclusion criteria, case–control studies with associations between BRMS1 and breast cancer were selected from articles obtained by way of searches conducted through an electronic database. All statistical analyses were performed with Stata 12.0 (Stata Corp, College Station, TX, U.S.A.). Ultimately, 1,263 patients with breast cancer were found in a meta-analysis retrieved from a total that included 12 studies. Results of our meta-analysis suggested that BRMS1 protein in breast cancer tissues was significantly lower in comparison with normal breast tissues (odds ratio, OR = 0.08, 95% confidence interval (CI) = 0.04–0.15). The BRMS1 protein in metastatic breast cancer tissue was decreased than from that was found in non-metastatic breast cancer tissue (OR = 0.20, 95%CI = 0.13–0.29), and BRMS1 protein in tumor-node-metastasis (TNM) stages 1 and 2 was found to be higher than TNM stages 3 and 4 (OR = 4.62, 95%CI = 2.77–7.70). BRMS1 protein in all three major types of breast cancer was lower than that of control tissues respectively. We also found strong correlations between BRMS1 mRNA levels and TNM stage and tumor size. The results our meta-analysis showed that reduction in BRMS1 expression level was linked directly to clinico-pathological features of breast cancer significantly; therefore, suggesting the loss of expression or reduced levels of BRMS1 is potentially a strong indicator of the metastatic capacity of breast cancer with poor prognosis.

Circulating Tumor Cells in HER-2 Positive Metastatic Breast Cancer Patients Treated with Trastuzumab and Chemotherapy

2009 ◽  
Vol 24 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Raquel A. Nunes ◽  
Xiaochun Li ◽  
Soonmo Peter Kang ◽  
Harold Burstein ◽  
Lisa Roberts ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Treatment Response ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Her 2

The detection of circulating tumor cells (CTCs) in peripheral blood may have important prognostic and predictive implications in breast cancer treatment. A limitation in this field has been the lack of a validated method of accurately measuring CTCs. While sensitivity has improved using RT-PCR, specificity remains a major challenge. The goal of this paper is to present a sensitive and specific methodology of detecting CTCs in women with HER-2-positive metastatic breast cancer, and to examine its role as a marker that tracks disease response during treatment with trastuzumab-containing regimens. The study included patients with HER-2-positive metastatic breast cancer enrolled on two different clinical protocols using a trastuzumab-containing regimen. Serial CTCs were measured at planned time points and clinical correlations were made. Immunomagnetic selection of circulating epithelial cells was used to address the specificity of tumor cell detection using cytokeratin 19 (CK19). In addition, the extracellular domain of the HER-2 protein (HER-2/ECD) was measured to determine if CTCs detected by CK19 accurately reflect tumor burden. The presence of CTCs at first restaging was associated with disease progression. We observed an association between CK19 and HER-2/ECD. The association of HER-2/ECD with clinical response followed a similar pattern to that seen with CK19. Finally, the absence of HER-2/ECD at best overall response and a change of HER-2/ECD from positive at baseline to negative at best overall response was associated with favorable treatment response. Our study supports the prognostic and predictive role of the detection of CTCs in treatment of HER-2-positive metastatic breast cancer patients. The association between CK19 and markers of disease burden is in line with the concept that CTCs may be a reliable measure of tumor cells in the peripheral blood of patients with metastatic breast cancer. The association of CTCs at first restaging with treatment failure indicates that CTCs may have a role as surrogate markers to monitor treatment response.

The association of HER2 low expression with the efficacy of CDK4/6 inhibitor in hormone receptor positive HER2 negative metastatic breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1052-1052
Author(s):  
Kelvin K H Bao ◽  
Leone Sutanto ◽  
Shirley S W Tse ◽  
Ka Man Cheung ◽  
Jeffrey C H Chan
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cox Regression ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Rank Test ◽  
Her2 Expression ◽  
Disease Extent ◽  
Potential Marker ◽  
Low Expression

1052 Background: Markers for the efficacy of CDK4/6 inhibitor in estrogen receptor (ER) positive, HER2 negative advanced breast cancer are limited. The bidirectional crosstalks that exist between ER and HER2 pathways contribute to endocrine resistance. We investigated the association between low levels of HER2 expression and the clinical outcome of patients with ER+ HER2- metastatic breast cancer (MBC) treated with CDK4/6 inhibitors. Methods: We identified consecutive patients with ER+ HER2- MBC who received CDK4/6 inhibitor plus either letrozole or fulvestrant between Mar 2017 - Jun 2020 from an institutional cancer registry. HER2-low expression was defined as IHC score 1+, or 2+ with a negative ISH. Progression-free survival (PFS) was defined as the time from the initiation of CDK4/6 inhibitor to the date of radiological or clinical progression, or death. The relationship between HER2 expression levels and PFS was evaluated using log-rank test and multivariable Cox regression modelling. Results: 106 women with MBC were eligible for analysis. Median age at treatment was 58 (23.0-91.4). The majority received palbociclib (84%) while the rest received ribociclib. CDK4/6 inhibitor was used as first-line treatment in 50.9% of cases. Most tumors were of ductal histology (83%) and progesterone receptor (PgR) positive (84.9%), and 22.6% of the patients had bone-only disease. 77.3% of cases were considered HER2-low expressing. HER2-low expression was associated with a significantly shorter PFS compared with HER2 IHC 0 counterpart (median, 8.9 vs 18.8 months, p= 0.014). In multivariate analysis, HER-2 low expression remained significantly associated with an inferior PFS (HR 1.96, 95%CI 1.03-3.75, p= 0.041) after adjusting for the line of treatment, PgR status and disease extent (bone only vs extra-osseous disease). Conclusions: In patients with ER+ HER2- MBC treated with CDK4/6 inhibitors, HER2-low expression was associated with an inferior PFS, and may serve as a potential marker candidate for CDK4/6 inhibitor efficacy. As novel anti-HER2 antibody-drug conjugates demonstrated efficacy in HER2-low expressing MBC, coupled with the emerging evidence for the combination of CDK4/6 inhibitors with anti-HER2 agents, this HER2-low expression subgroup warrants prospective evaluations in future trials.

scholarly journals Survival impact of primary tumor resection in de novo metastatic breast cancer patients (GEICAM/El Alamo Registry)

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sara Lopez-Tarruella ◽  
M. J. Escudero ◽  
Marina Pollan ◽  
Miguel Martín ◽  
Carlos Jara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Primary Tumor ◽  
Cox Regression ◽  
De Novo ◽  
Histological Grade ◽  
Tumor Resection ◽  
Metastatic Breast ◽  
Breast Cancer Patients

AbstractThe debate about surgical resection of primary tumor (PT) in de novo metastatic breast cancer (MBC) patients persists. We explored this approach’s outcomes in patients included in a retrospective registry, named El Álamo, of breast cancer patients diagnosed in Spain (1990–2001). In this analysis we only included de novo MBC patients, 1415 of whom met the study’s criteria. Descriptive, Kaplan-Meier and Cox regression analyses were carried out. Median age was 63.1 years, 49.2% of patients had single-organ metastasis (skin/soft tissue [16.3%], bone [33.8%], or viscera [48.3%]). PT surgery (S) was performed in 44.5% of the cases. S-group patients were younger, had smaller tumors, higher prevalence of bone and oligometastatic disease, and lower prevalence of visceral involvement. With a median follow-up of 23.3 months, overall survival (OS) was 39.6 versus 22.4 months (HR = 0.59, p < 0.0001) in the S- and non-S groups, respectively. The S-group OS benefit remained statistically and clinically significant regardless of metastatic location, histological type, histological grade, hormone receptor status and tumor size. PT surgery (versus no surgery) was associated with an OS benefit suggesting that loco-regional PT control may be considered in selected MBC patients. Data from randomized controlled trials are of utmost importance to confirm these results.

scholarly journals Exploratory analysis of circulating cytokines in patients with metastatic breast cancer treated with eribulin: the TRANSERI-GONO (Gruppo Oncologico del Nord Ovest) study

ESMO Open ◽  
2020 ◽  
Vol 5 (5) ◽  
pp. e000876 ◽  
Author(s):  
Ornella Garrone ◽  
Andrea Michelotti ◽  
Matteo Paccagnella ◽  
Filippo Montemurro ◽  
Anna Maria Vandone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Tumour Microenvironment ◽  
Exploratory Analysis ◽  
Cox Regression Analysis ◽  
Circulating Cytokines

BackgroundAnticancer drugs can interact with the tumour microenvironment and their effects could be exploited to favour anticancer immune response. Eribulin contributes to tumour vasculature remodelling and transforming growth factor β (TGF-β) modulation in experimental models and in humans. We performed a prospective, translational, exploratory analysis of the levels of circulating cytokines at different time points in patients with metastatic breast cancer treated with eribulin.MethodsTGF-β, tumour necrosis factor α, vascular endothelial growth factor, IL-6, IL-8, IL-10, IL-21 and C-C motif chemokine ligand-2 levels were assessed in peripheral blood samples obtained from seven healthy volunteers and 41 patients at baseline (T0), after four cycles of eribulin (T1) and at disease progression (TPD). Baseline values and longitudinal changes in cytokine levels were then related to clinical outcome.ResultsIn the 41 patients, high IL-6 and IL-8 (above the median) at T0 significantly correlated with worse survival. At T1, IL-21 significantly decreased in patients with TPD within the fourth course of treatment, compared with patients without progression. TGF-β and IL-8 above the median and IL-21 below the median at T1 significantly correlates with worse progression free survival (PFS). Patients exhibiting an increase of TGF-β or a decline of IL-21 between T0 and T1 showed a significantly worse PFS. Multivariate Cox regression analysis showed that only plasma TGF-β changes at T1 correlated with survival. At TPD, TGF-β significantly increased in all patients.ConclusionsWe observed a significant correlation between TGF-β decline during eribulin treatment and outcome in patients with metastatic breast cancer. Altogether, our data suggest that eribulin treatment might interfere with the tumour microenvironment.

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