35 research outputs found
Targeted therapy for metastatic triple negative breast cancer: The next frontier in precision oncology
No full textMetadata supporting data files in the published article: Androgen receptor gene expression in primary breast cancer: correlations with clinical features, tumor characteristics, patient outcomes, and other breast-cancer related genes
No full textIn this paper, the authors studied
androgen receptor (AR) gene expression in primary breast cancer (BC) to
determine associations with clinical characteristics and outcomes in the I-SPY
1 (Investigation of Serial Studies to Predict Your Therapeutic Response With
Imaging and Molecular Analysis) study.
Data
access: The study used publically available datasets. I-SPY 1 datasets were accessed from the NCBI
Gene Expression Omnibus (GEO) repository: https://identifiers.org/geo:GSE22226. TCGA gene expression data were accessed from
the cBioPortal for Cancer Genomics: https://identifiers.org/cbioportal:brca_tcga_pub2015. METABRIC gene expression data were accessed
from the European Genome-phenome Archive (EGA): https://identifiers.org/ega.dataset:EGAD00010000210 and https://identifiers.org/ega.dataset:EGAD00010000211.
Study aims
and methodology: The purpose of this study was to examine
androgen receptor (AR) gene expression in primary breast cancer (BC) to
determine associations with clinical characteristics and outcomes in the I-SPY
1 study.
AR was evaluated in I-SPY 1 (n=149)
using expression microarrays. Associations of AR with clinical and tumor
features were determined using the Wilcoxon rank sum test or the Kruskal-Wallis
test. The authors identified an optimal AR cut-point to maximize recurrence-free survival
(RFS) differences between AR biomarker stratified groups, and assessed the
association between the AR stratified groups and RFS using the Cox proportional
hazard model. Pearson correlations between AR and selected genes were
determined in I-SPY 1, METABRIC (n=1992), and TCGA (n=817).
Datasets
supporting the figures and tables in the published article:
Dataset
names, formats and persistent links to datasets are provided in the file Vidula et al.xlsx</p
Translating the Molecular Message of Triple-Negative Breast Cancer into Targeted Therapy
No full textCyclin-Dependent Kinase 4/6 Inhibitors for the Treatment of Breast Cancer: A Review of Preclinical and Clinical Data
No full textEmerging data on improving response to hormone therapy: the role of novel targeted agents
No full textUltrasound accelerated bone tissue engineering monitored with magnetic resonance microscopy.
No full textTissue engineering has the potential to treat bone loss, but current bone restoration methods, including osteogenesis from mesenchymal stem cells (MSCs), require three to four weeks for bone formation to occur. In this study, we stimulated the formation of engineered bone tissue with low-intensity ultrasound, which has been proven to accelerate bone healing in vivo. One group of engineered bone constructs received ultrasound stimulation 20 minutes per day over a 3-week growth period. We monitored the growth of all the engineered constructs quantitatively and noninvasively using magnetic resonance microscopy (MRM), where the T2 relaxation times of all the constructs were measured, on a weekly basis, using an 11.74 T Bruker spectrometer. Histological and immunocytochemical sections were obtained for all constructs and correlated with the MR results. This study shows that ultrasound can accelerate osteogenesis in vitro for tissue engineered bone, the growth and development of which can be monitored using MRM
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Androgen receptor gene expression in primary breast cancer
No full textWe studied androgen receptor (AR) gene expression in primary breast cancer (BC) to determine associations with clinical characteristics and outcomes in the I-SPY 1 study. AR was evaluated in I-SPY 1 (n = 149) using expression microarrays. Associations of AR with clinical and tumor features were determined using the Wilcoxon rank sum test (two-level factors) or the Kruskal-Wallis test (multi-level factors). We identified an optimal AR cut-point to maximize recurrence-free survival (RFS) differences between AR biomarker stratified groups, and assessed the association between the AR stratified groups and RFS using the Cox proportional hazard model. Pearson correlations between AR and selected genes were determined in I-SPY 1, METABRIC (n = 1992), and TCGA (n = 817). AR was lower in triple negative BC vs. hormone receptor positive (HR+)/HER2- and HER2+ disease (p < 0.00001), and lower in basal-like BC (p < 0.00001). AR was higher in grade I/II vs. III tumors (p < 0.00001), in patients >age 50 (p = 0.05), and in node negative disease (p = 0.006). Higher AR was associated with better RFS (p = 0.0007), which remained significant after receptor subtype adjustment (p = 0.01). AR correlated with expression of luminal, HER2, and steroid hormone genes. AR expression was related to clinicopathologic features, intrinsic subtype, and correlated with improved outcome
Receptor activator of nuclear factor kappa B (RANK) expression in primary breast cancer correlates with recurrence-free survival and development of bone metastases in I-SPY1 (CALGB 150007/150012; ACRIN 6657)
No full textPurposeThe receptor activator of nuclear factor kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) axis may contribute to the development of bone metastases (BM). We studied gene expression in this pathway in primary breast cancer (BC) to determine correlations with clinical characteristics and outcomes in the neoadjuvant I-SPY1 study.MethodsWe evaluated RANK/RANKL/OPG expression using expression microarrays in I-SPY1 (n = 149). Associations with clinical features were determined using t test and ANOVA. Associations between biomarker high versus low groups (dichotomized at an optimal cutpoint) and recurrence-free survival (RFS) were evaluated using the log-rank test and in a multivariate Cox proportional hazard model. A pooled external neoadjuvant cohort with gene expression data (GSE25066) (Hatzis et al. in JAMA 305(18):1873-1881, 30) (n = 425) was used for validation. Associations with site-specific relapse were evaluated using the t-test and multivariate logistic regression adjusting for hormone receptor (HR) status.ResultsRANK was significantly higher in HR negative versus HR positive (p = 0.027), in basal versus non-basal disease (p = 0.004), and in those achieving pathologic complete response (p = 0.038); the associations with HR negative and basal BC were also significant in GSE25066. In both datasets, higher RANK associated with significantly worse RFS (I-SPY1: p = 0.045, GSE25066: p = 0.044). However, this association did not remain significant after adjusting for HR status. In I-SPY1 patients with recurrence, higher RANK correlated with BM versus non-BM (p = 0.045), even after adjusting for HR status (p = 0.035).ConclusionsRANK is increased in HR negative and basal BC, and correlates with worse RFS and risk of BM. The RANK pathway is a potential therapeutic target in BC
