scholarly journals Abstract 5008: The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation

2017 ◽  
Author(s):  
Gino B. Ferraro ◽  
David P. Kodack ◽  
Vasileios Askoxylakis ◽  
Qing Sheng ◽  
Mark Badeaux ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Luminal Breast Cancer ◽  
Pi3k Inhibition ◽  
The Brain

scholarly journals The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation

2017 ◽  
Vol 9 (391) ◽  
pp. eaal4682 ◽  
Author(s):  
David P. Kodack ◽  
Vasileios Askoxylakis ◽  
Gino B. Ferraro ◽  
Qing Sheng ◽  
Mark Badeaux ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Treatment Strategies ◽  
Brain Lesions ◽  
Growth Delay ◽  
Luminal Breast Cancer ◽  
Pi3k Inhibition ◽  
Mechanistic Basis ◽  
Breast Cancer Brain Metastases ◽  
The Brain

Although targeted therapies are often effective systemically, they fail to adequately control brain metastases. In preclinical models of breast cancer that faithfully recapitulate the disparate clinical responses in these microenvironments, we observed that brain metastases evade phosphatidylinositide 3-kinase (PI3K) inhibition despite drug accumulation in the brain lesions. In comparison to extracranial disease, we observed increased HER3 expression and phosphorylation in brain lesions. HER3 blockade overcame the resistance ofHER2-amplified and/orPIK3CA-mutant breast cancer brain metastases to PI3K inhibitors, resulting in marked tumor growth delay and improvement in mouse survival. These data provide a mechanistic basis for therapeutic resistance in the brain microenvironment and identify translatable treatment strategies forHER2-amplified and/orPIK3CA-mutant breast cancer brain metastases.

Rab11 family-interacting protein 4, RAB11FIP4, is a differentially expressed gene in brain metastatic human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Differentially Expressed Gene ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Interacting Protein ◽  
Primary Tumors ◽  
Free Survival ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that Rab11 family-interacting protein 4, encoded by RAB11FIP4, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. RAB11FIP4 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of RAB11FIP4 in primary tumors was significantly correlated with patient recurrence-free survival and distant metastasis-free survival. Modulation of RAB11FIP4 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.

Correlation of AGR2 expression with the incidence of metastasis in luminal breast cancer

2021 ◽  
pp. 1-5
Author(s):  
David Samuel Kereh ◽  
John Pieter ◽  
William Hamdani ◽  
Haryasena Haryasena ◽  
Daniel Sampepajung ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Mean Value ◽  
Rank Test ◽  
Luminal Breast Cancer ◽  
P Value ◽  
Strong Positive Correlation ◽  
Breast Cancer Patients ◽  
The Mean ◽  
Spearman Test

BACKGROUND: AGR2 expression is associated with luminal breast cancer. Overexpression of AGR2 is a predictor of poor prognosis. Several studies have found correlations between AGR2 in disseminated tumor cells (DTCs) in breast cancer patients. OBJECTIVE: This study aims to determine the correlation between anterior Gradient2 (AGR2) expression with the incidence of distant metastases in luminal breast cancer. METHODS: This study was an observational study using a cross-sectional method and was conducted at Wahidin Sudirohusodo Hospital and the network. ELISA methods examine AGR2 expression from blood serum of breast cancer patients. To compare the AGR2 expression in metastatic patients and the non-metastatic patient was tested with Mann Whitney test. The correlation of AGR2 expression and metastasis was tested with the Rank Spearman test. RESULTS: The mean value of AGR2 antibody expression on ELISA in this study was 2.90 ± 1.82 ng/dl, and its cut-off point was 2.1 ng/dl. Based on this cut-off point value, 14 subjects (66.7%) had overexpression of AGR2 serum ELISA, and 7 subjects (33.3%) had not. The mean value AGR2 was significantly higher in metastatic than not metastatic, 3.77 versus 1.76 (p < 0.01). The Spearman rank test obtained a p-value for the 2 tail test of 0.003 (p < 0.05), which showed a significant correlation of both, while the correlation coefficient of 0.612 showed a strong positive correlation of AGR2 overexpression and metastasis. CONCLUSIONS: AGR2 expression is correlated with metastasis in Luminal breast cancer.

scholarly journals Prognostic Relevance of Neutrophil to Lymphocyte Ratio (NLR) in Luminal Breast Cancer: A Retrospective Analysis in the Neoadjuvant Setting

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1685
Author(s):  
Antonino Grassadonia ◽  
Vincenzo Graziano ◽  
Laura Iezzi ◽  
Patrizia Vici ◽  
Maddalena Barba ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Post Treatment ◽  
Neutrophil To Lymphocyte Ratio ◽  
Luminal Breast Cancer ◽  
Luminal A ◽  
Luminal B ◽  
Lymphocyte Ratio ◽  
Cell Counts ◽  
Pre Treatment

The neutrophil to lymphocyte ratio (NLR) is a promising predictive and prognostic factor in breast cancer. We investigated its ability to predict disease-free survival (DFS) and overall survival (OS) in patients with luminal A- or luminal B-HER2-negative breast cancer who received neoadjuvant chemotherapy (NACT). Pre-treatment complete blood cell counts from 168 consecutive patients with luminal breast cancer were evaluated to assess NLR. The study population was stratified into NLRlow or NLRhigh according to a cut-off value established by receiving operator curve (ROC) analysis. Data on additional pre- and post-treatment clinical-pathological characteristics were also collected. Kaplan–Meier curves, log-rank tests, and Cox proportional hazards models were used for statistical analyses. Patients with pre-treatment NLRlow showed a significantly shorter DFS (HR: 6.97, 95% CI: 1.65–10.55, p = 0.002) and OS (HR: 7.79, 95% CI: 1.25–15.07, p = 0.021) compared to those with NLRhigh. Non-ductal histology, luminal B subtype, and post-treatment Ki67 ≥ 14% were also associated with worse DFS (p = 0.016, p = 0.002, and p = 0.001, respectively). In a multivariate analysis, luminal B subtype, post-treatment Ki67 ≥ 14%, and NLRlow remained independent prognostic factors for DFS, while only post-treatment Ki67 ≥ 14% and NLRlow affected OS. The present study provides evidence that pre-treatment NLRlow helps identify women at higher risk of recurrence and death among patients affected by luminal breast cancer treated with NACT.

Cytokeratin 7, GATA3, and SOX-10 is a Comprehensive Panel in Diagnosing Triple Negative Breast Cancer Brain Metastases

2021 ◽  
pp. 106689692199071
Author(s):  
Eric Statz ◽  
Julie M. Jorns
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metastatic Tumor ◽  
Cytokeratin 7 ◽  
Breast Cancer Metastases ◽  
Her2 Breast Cancer ◽  
Cancer Metastases ◽  
Breast Cancer Brain Metastasis ◽  
The Brain

Following lung cancer, breast cancer is the second most common metastatic tumor to the brain, of which triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2+ (HER2+) breast cancer are the most common subtypes. TNBC does not have standard immunoprofiles and can be difficult to distinguish from other metastases. A tissue microarray was created from 47 patients with breast cancer metastases to the brain and 12 paired breast primaries. Of 47 breast cancer metastases, 24 were HER2+, 14 were TNBC, and 9 were luminal. Forty-five were cytokeratin 7 (CK7) positive, 36 were GATA-binding protein 3 (GATA3) positive, 7 were Sry-related HMg-Box gene 10 (SOX-10) positive, 20 were mammaglobin positive, and 19 were gross cystic disease fluid protein 15 positive. At least one of the CK7, GATA3, or SOX-10 was positive in all TNBC metastases. A panel of CK7, GATA3, and SOX-10 is complementary in the diagnosis of breast cancer brain metastasis. SOX-10 appears to be a specific but not particularly sensitive marker in this context.

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