scholarly journals GIRK1 overexpression correlates with ER positive breast cancer subtypes and is associated with poor prognosis

2015 ◽  
Vol 26 ◽  
pp. iii15 ◽  
Author(s):  
S. Kammerer ◽  
A. Sokolowski ◽  
H. Hackl ◽  
D. Platzer ◽  
S. Jahn ◽  
...  
2020 ◽  
Author(s):  
Ai Amioka ◽  
Takayuki Kadoya ◽  
Satoshi Sueoka ◽  
Yoshie Kobayashi ◽  
Shinsuke Sasada ◽  
...  

Abstract BackgroundIt was previously reported by us that Wnt5a-positive breast cancer can be classified as estrogen receptor (ER)-positive breast cancer and its prognosis is worse than that of Wnt5a-negative breast cancer. Herein, the molecular mechanisms underlying the poor prognosis of Wnt5a-positive breast cancer patients were examined. MethodsA total of 151 consecutive ER-positive breast cancer patients who underwent resection between January 2011 and February 2014 were enrolled. DNA microarray and pathway analyses were performed conducted using MCF-7 cells stably expressing Wnt5a (MCF-7/Wnt5a(+)). Based on the results, cell viability and drug sensitivity assays as well as mutation analysis , were performed using culture cells and breast cancer tissue. The relationship between Wnt5a and the PI3K–AKT–mTOR signaling pathway was examined.ResultsThe relapse-free survival rate in patients with Wnt5a-positive breast cancer was significantly lower than that in patients with Wnt5a-negative breast cancer ( P = 0.047). DNA microarray data indicated that only the cytochrome P450 (CYP) pathway was significantly upregulated in MCF-7/Wnt5a(+) cells ( P = 0.0440). MCF-7/Wnt5a(+) cells showed reduced sensitivity to the metabolic substrates of CYP, tamoxifen ( P < 0.001), and paclitaxel ( P < 0.001). PIK3CA mutations were unrelated to Wnt5a expression in breast cancer tissue and culture cells.ConclusionsIn ER-positive breast cancer, Wnt5a upregulated the CYP metabolic pathway; additionally, it inhibited the sensitivity to tamoxifen and paclitaxel, which constitute the standard treatment options for ER-positive breast cancer. Wnt5a could be involved in the poor prognosis of ER-positive breast cancer independently of the PI3K–AKT–mTOR signaling pathway.


Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2618 ◽  
Author(s):  
Samantha A Hutchinson ◽  
Priscilia Lianto ◽  
Hanne Roberg-Larsen ◽  
Sebastiano Battaglia ◽  
Thomas A Hughes ◽  
...  

Interventions that alter cholesterol have differential impacts on hormone receptor positive- and negative-breast cancer risk and prognosis. This implies differential regulation or response to cholesterol within different breast cancer subtypes. We evaluated differences in side-chain hydroxycholesterol and liver X nuclear receptor signalling between Oestrogen Receptor (ER)-positive and ER-negative breast cancers and cell lines. Cell line models of ER-positive and ER-negative disease were treated with Liver X Receptor (LXR) ligands and transcriptional activity assessed using luciferase reporters, qPCR and MTT. Publicly available datasets were mined to identify differences between ER-negative and ER-positive tumours and siRNA was used to suppress candidate regulators. Compared to ER-positive breast cancer, ER-negative breast cancer cells were highly responsive to LXR agonists. In primary disease and cell lines LXRA expression was strongly correlated with its target genes in ER-negative but not ER-positive disease. Expression of LXR’s corepressors (NCOR1, NCOR2 and LCOR) was significantly higher in ER-positive disease relative to ER-negative, and their knock-down equalized sensitivity to ligand between subtypes in reporter, gene expression and viability assays. Our data support further evaluation of dietary and pharmacological targeting of cholesterol metabolism as an adjunct to existing therapies for ER-negative and ER-positive breast cancer patients.


2021 ◽  
Author(s):  
Toshiki Kazama ◽  
Taro Takahara ◽  
Thomas C. Kwee ◽  
Noriko Nakamura ◽  
Nobue Kumaki ◽  
...  

Abstract Purpose To correlate quantitative T1, T2, and proton density (PD) values from synthetic MRI with breast cancer subtypes. Methods Twenty-eight breast cancer patients underwent MRI of the breast including synthetic MRI. T1, T2, and PD values were correlated with Ki-67. T1, T2, and PD values were compared between estrogen receptor (ER) positive and ER negative cancers, and between Luminal A and Luminal B cancers. The effectiveness of T1, T2, and PD in differentiating the ER-negative from the ER-positive group and Luminal A from Luminal B cancers was evaluated using receiver operating characteristic analysis.Results Mean T2 relaxation of ER-negative cancers was significantly higher than that of ER-positive cancers (p < .05). The T1, T2, and PD values exhibited a strong positive correlation with Ki-67 (Pearson's r = 0.75, 0.69, and 0.60 respectively; p < .001). Among ER-positive cancers (n=23), T1, T2, and PD values of Luminal A cancers were significantly lower than those of Luminal B cancers (p < .05). The areas under the curve (AUCs) of T1, T2, and PD for discriminating ER-negative from ER-positive cancers were 0.74 (95% confidence interval (CI): 0.54-0.88), 0.87 (95% CI: 0.69-0.97), and 0.62 (95% CI: 0.42-0.79), respectively. The AUCs of T1, T2, and PD values for discriminating Luminal A from Luminal B cancers were 0.83 (95% CI: 0.61-0.95), 0.75 (95% CI: 0.52-0.90), and 0.75 (95% CI: 0.53-0.91), respectively.Conclusion Quantitative values from synthetic MRI significantly correlate with subtypes of invasive breast cancers and may classify subtypes with reasonably good accuracy.


2010 ◽  
Vol 8 (5) ◽  
pp. 92-93
Author(s):  
A. Hendrix ◽  
W. Westbroek ◽  
V. Cocquyt ◽  
M. Bracke ◽  
O. De Wever

ESMO Open ◽  
2020 ◽  
Vol 5 (5) ◽  
pp. e000829
Author(s):  
Mariana Brandão ◽  
Assucena Guisseve ◽  
Genoveva Bata ◽  
Matos Alberto ◽  
Josefo Ferro ◽  
...  

BackgroundData regarding breast cancer epidemiology, treatment and survival in Africa are scarce. We aimed to assess the distribution of breast cancer subtypes in Mozambique and its impact on patients’ treatment and survival. The concordance of biomarker assessment between cytological and histological samples was also evaluated.MethodsProspective cohort study including 210 patients diagnosed between January 2015 and August 2017, followed to November 2019. Clinicopathological characteristics, treatment, 3-year overall survival (OS) and disease-free survival (DFS) were compared across classic tumour subtypes (oestrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, HER2-positive and triple-negative breast cancer (TNBC)) and surrogate intrinsic subtypes (St. Gallen classification). Concordance was measured using Cohen’s κ statistics.ResultsA total of 51% of patients had ER-positive/HER2-negative tumours, 24% HER2-positive and 25% TNBC. Concordance between cytological and histological samples regarding ER and HER2 status was substantial (κ=0.762 and κ=0.603, respectively). There were no significant differences across subtypes regarding clinical characteristics and treatment, except for HIV positivity and high histological grade (more prevalent among TNBC) or endocrine therapy (higher use among ER-positive/HER2-negative and HER2-positive patients). Three-year OS was 52.5% (95% CI, 44.3% to 60.0%), being higher in ER-positive/HER2-negative (61.1%) compared with HER2-positive (53.2%) and TNBC (31.9%) patients. Adjusted HRs were 1.96 (95% CI, 1.13 to 3.39) among HER2-positive and 3.10 (95% CI, 1.81 to 5.31) among TNBC versus ER-positive/HER2-negative patients. Three-year DFS was 46.6% (95% CI, 38.0% to 54.8%), being lower among TNBC versus ER-positive/HER2-negative patients (HR 2.91; 95% CI, 1.64 to 5.16). Results were similar between surrogate intrinsic subtypes.ConclusionThere was a high proportion of HER2-positive and TNBC among Mozambican patients and their survival was poor compared with ER-positive/HER2-negative patients, partly due to the limited treatment options. A systematic assessment of ER, PR and HER2 status is feasible and may help tailoring and optimise the treatment of patients with breast cancer in low-resource settings, potentially leading to survival gains in this underserved population.


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