Abstract PS18-01: Glucocorticoid receptor expression in early-stage triple-negative breast cancer is associated with a high level of tumor immune cell infiltrates

2021 ◽  
Author(s):  
Deniz N Dolcen ◽  
Marie Dreyer ◽  
Aaron Miller ◽  
Anna Biernacka ◽  
Ken Hatogai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucocorticoid Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Immune Cell ◽  
Early Stage ◽  
Receptor Expression ◽  
High Level ◽  
Immune Cell Infiltrates

scholarly journals Immunhistochemical Assessment of PD-L1 Expression Using Three Different Monoclonal Antibodies in Triple Negative Breast Cancer Patients

2021 ◽  
Author(s):  
Gilda Schmidt ◽  
Margit Maria Guhl ◽  
Erich-Franz Solomayer ◽  
Gudrun Wagenpfeil ◽  
Mohammed Eid Hammadeh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Monoclonal Antibodies ◽  
Tumor Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Immune Cell ◽  
Receptor Expression ◽  
Cancer Tissue ◽  
Tissue Samples ◽  
Ki67 Expression

Abstract Background: PD-L1 receptor expression in breast cancer tissue can be assessed with different anti-human PD-L1 monoclonal antibodies. The performance of three specific monoclonal antibodies in a head-to-head comparison is unknown. Also, a potential correlation of PD-L1 expression and clinico-pathological parameters has not been investigated.MethodsThis was a retrospective study on tissue samples of patients with histologically confirmed triple negative breast cancer (TNBC). PD-L1 receptors were immune histochemically stained with three anti-human PD-L1 monoclonal antibodies: 22C3 and 28-8 for staining of tumor cell membranes (TC) and cytoplasm (Cyt), SP142 for immune cell staining (IC).Three different tissue samples of each patient were evaluated separately by two observers in a blinded fashion. The percentage of PD-L1 positive tumor cells in relation to the total number of tumor cells was determined. For antibodies 22C3 and 28-8 PD-L1 staining of 0 to <1% of tumor cells was rated "negative", 1 to 50% was rated "positive" and > 50% was rated "strong positive". Cyt staining was defined as “negative” when no signal was observed and as “positive”, when any positive signal was observed. For IC staining with SP142 all samples with PD-L1 expression ≥1% were rated as “positive”. Finally, the relationship between PD-L1 expression and clinico-pathological parameters was analyzed.Results Tissue samples from 59 of 60 enrolled patients could be analyzed. Mean age was 55 years. Both the monoclonal antibodies 22C3 and 28-8 had similar properties, and were positive for both TC in 13 patients (22%) and for Cyt staining in 24 patients (40.7%). IC staining with antibody SP142 was positive in 24 patients (40.7%), who were also positive for Cyt staining. The differences between TC and Cyt staining and TC and IC staining were significant (p=0.001). Cases with positive TC staining showed higher Ki67 expression compared to those with negative staining, 40% vs 30%, respectively (p=0.05). None of the other clinico-pathological parameters showed any correlation with PDL1 expression. ConclusionAntibodies 22C3 and 28-8 can be used interchangeably for PD-L1 determination in tumor cells of TNBC patients. Results for Cyt staining with 22C3 or 28-8 and IC staining with SP142 were identical. PD-L1 expression correlates with Ki67 expression but not with OS or DFS.

Androgen Receptor Expression Predicts Decreased Survival in Early Stage Triple-Negative Breast Cancer

2014 ◽  
Vol 22 (1) ◽  
pp. 82-89 ◽  
Author(s):  
Jung Eun Choi ◽  
Su Hwan Kang ◽  
Soo Jung Lee ◽  
Young Kyung Bae
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Receptor Expression ◽  
Androgen Receptor Expression

scholarly journals Glucocorticoid Receptor Expression Predicts Good Outcome in response to Taxane-Free, Anthracycline-Based Therapy in Triple Negative Breast Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ahmed Elkashif ◽  
Victoria Bingham ◽  
Paula Haddock ◽  
Matthew P. Humphries ◽  
Stephen McQuaid ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucocorticoid Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Standard Of Care ◽  
Predictive Biomarker ◽  
Receptor Expression ◽  
Breast Cancers ◽  
Current Standard ◽  
Poor Outcome

Triple negative breast cancer (TNBC) is a poor outcome subset of breast cancers characterised by the lack of expression of ER α, PR, and HER2 amplification. It is a heterogeneous group of cancers which fail to derive benefit from modern, more targeted treatments such as Tamoxifen and Herceptin. Current standard of care (SoC) is cytotoxic chemotherapy, which is effective for some patients, with other patients deriving little/no benefit and lacking alternative treatments. This study has identified the glucocorticoid receptor (GR) as a potential predictive biomarker of response to anthracycline-based chemotherapy in triple negative breast cancer (TNBC). GR gene expression levels in patient samples were analysed through publicly available microarray datasets as well as protein expression through immunohistochemistry (IHC) and correlated with clinical/pathological outcomes, including survival. While the results confirmed previous observations that high GR expression is associated with poor outcome in response to taxane-based chemotherapy, this study shows for the first time that high GR expression is associated with improved outcomes in the context of anthracycline-based chemotherapy. GR therefore has the potential to be used as a predictive biomarker to guide treatment choices and ensure that patients derive the greatest benefit from first line treatment, avoiding unnecessary costs, side effects, and disease progression.

scholarly journals MiR-211 determines brain metastasis specificity through SOX11/NGN2 axis in triple-negative breast cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Jhih-Kai Pan ◽  
Cheng-Han Lin ◽  
Yao-Lung Kuo ◽  
Luo-Ping Ger ◽  
Hui-Chuan Cheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Survival Outcomes ◽  
Poor Survival ◽  
Breast Cancer Brain Metastasis ◽  
High Level

AbstractBrian metastasis, which is diagnosed in 30% of triple-negative breast cancer (TNBC) patients with metastasis, causes poor survival outcomes. Growing evidence has characterized miRNAs involving in breast cancer brain metastasis; however, currently, there is a lack of prognostic plasma-based indicator for brain metastasis. In this study, high level of miR-211 can act as brain metastatic prognostic marker in vivo. High miR-211 drives early and specific brain colonization through enhancing trans-blood–brain barrier (BBB) migration, BBB adherence, and stemness properties of tumor cells and causes poor survival in vivo. SOX11 and NGN2 are the downstream targets of miR-211 and negatively regulate miR-211-mediated TNBC brain metastasis in vitro and in vivo. Most importantly, high miR-211 is correlated with poor survival and brain metastasis in TNBC patients. Our findings suggest that miR-211 may be used as an indicator for TNBC brain metastasis.

321 Phase I clinical trial assessing the combination of systemic chemokine modulatory regimen targeting TLR3 with neoadjuvant chemotherapy in triple negative breast cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A347-A347
Author(s):  
Shipra Gandhi ◽  
Mateusz Opyrchal ◽  
Cayla Ford ◽  
Victoria Fitzpatrick ◽  
Melissa Grimm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Phase I ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Standard Dose ◽  
Surrogate Marker ◽  
Comprehensive Cancer Center ◽  
Cancer Center

BackgroundNeoadjuvant chemotherapy (NAC) with taxanes is the standard of care in triple negative breast cancer (TNBC). Intratumoral prevalence of CD8+ cytotoxic T-lymphocytes (CTLs) is associated with an improvement in relapse-free survival (RFS) and overall survival (OS), while regulatory T-cells (Treg) and myeloid derived suppressor cells (MDSC) are associated with poor survival. Higher ratio of CTL/Treg is associated with higher probability of obtaining pathological complete response (pCR), a surrogate marker for RFS. Intratumoral production of CCL5, CXCL9, CXCL10 and CXCL11 is critical for local infiltration with CTLs, while CCL22 is responsible for Treg attraction. Previous studies have shown that CXCL9 expression in the pre-treatment breast tissue is associated with a three-fold higher rate of achieving pCR. Our preclinical data show that Chemokine modulating (CKM) regimen, combining rintatolimod (TLR3 agonist), interferon (IFN)-α2b, and celecoxib (COX-2 inhibitor) increases CTL-attracting, and decreases MDSC-, Treg-favoring chemokines, increasing CTL/Treg ratio in tumor microenvironment, with preferential tumor tissue activation than adjacent healthy tissues. We hypothesize that the combination of CKM with paclitaxel will result in infiltration of TNBC with CTLs, and along with doxorubicin/cyclophosphamide (AC), result in higher pCR, translating into improved RFS and OS.MethodsIn this phase I study NCT04081389, eligibility includes age ≥18 years, confirmed resectable TNBC, radiographically measurable disease ≥1 cm, ECOG PS ≤ 2, adequate organ and marrow function. Patients with autoimmune disease, serious mood disorders, invasive carcinoma within 3 years, history of peptic ulcers or hypersensitivity to NSAIDs will be excluded. We plan to treat three patients with early stage TNBC with paclitaxel 80 mg/m2 IV weekly for 12 weeks, rintatolimod 200 mg IV, celecoxib 200 mg oral twice daily, and accelerated titration of IFN-α2b at doses 0, 5, or 10 million units (MU)/m2 [Dose Levels (DL) 1, 2 and 3 respectively] on days 1–3 (no intra-patient dose escalation) in weeks 1–3. Dose-limiting toxicity (DLT) is defined as grade 3 or higher toxicities within the first 3 weeks. Any DLT will mandate recruitment per the 3+3 model. If no DLT, three patients will be enrolled at DL 4 at 20 MU/m2 IFN- α2b. This will be followed by standard dose-dense AC, and then surgery. The primary endpoint is safety and tolerability of combination and to identify the appropriate DL of CKM and paclitaxel for extended efficacy study. The secondary endpoints include investigation of efficacy (pCR and breast MRI response), along with RFS and OS. Intratumoral biomarkers will be analyzed in an exploratory manner.ResultsN/AConclusionsN/ATrial RegistrationNCT04081389Ethics ApprovalThe study was approved by Roswell Park Comprehensive Cancer Center Institution’s Ethics Board, approval number I-73718.

Adjuvant addition of capecitabine to early-stage triple-negative breast cancer patients receiving standard chemotherapy: a meta-analysis

2019 ◽  
Vol 179 (3) ◽  
pp. 533-542 ◽  
Author(s):  
Yan Li ◽  
Yidong Zhou ◽  
Feng Mao ◽  
Yan Lin ◽  
Xiaohui Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Meta Analysis ◽  
Breast Cancer Patients ◽  
Standard Chemotherapy

scholarly journals Upregulation of IL15RA in Triple Negative Breast Cancer (TNBC) Promotes Tumour Cell Growth and Motility and Can Activate an Immune Cell Response

2013 ◽  
Vol 24 ◽  
pp. iii38
Author(s):  
P. Marra ◽  
S. Mathew ◽  
A. Grigoriadis ◽  
Y. Wu ◽  
F. Kyle-Cezar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Triple Negative Breast Cancer ◽  
Tumour Cell ◽  
Cell Response ◽  
Triple Negative ◽  
Immune Cell ◽  
Immune Cell Response ◽  
Tumour Cell Growth
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