scholarly journals The role of the AR/ER ratio in ER-positive breast cancer patients

2018 ◽  
Vol 25 (3) ◽  
pp. 163-172 ◽  
Author(s):  
Nelson Rangel ◽  
Milena Rondon-Lagos ◽  
Laura Annaratone ◽  
Simona Osella-Abate ◽  
Jasna Metovic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Histological Grade ◽  
Molecular Characteristics ◽  
Prognostic Impact ◽  
Breast Cancer Patients ◽  
Disease Free Interval ◽  
Hazard Ratios ◽  
Er Positive ◽  
Independent Marker

The significance of androgen receptor (AR) in breast cancer (BC) management is not fully defined, and it is still ambiguous how the level of AR expression influences oestrogen receptor-positive (ER+) tumours. The aim of the present study was to analyse the prognostic impact of AR/ER ratio, evaluated by immunohistochemistry (IHC), correlating this value with clinical, pathological and molecular characteristics. We retrospectively selected a cohort of 402 ER+BC patients. On each tumour, IHC analyses for AR, ER, PgR, HER2 and Ki67 were performed and AR+ cases were used to calculate the AR/ER value. A cut-off of ≥2 was selected using receiver-operating characteristic (ROC) curve analyses. RNA from 19 cases with AR/ER≥2 was extracted and used for Prosigna-PAM50 assays. Tumours with AR/ER≥2 (6%) showed more frequent metastatic lymph nodes, larger size, higher histological grade and lower PgR levels than cases with AR/ER<2. Multivariate analysis confirmed that patients with AR/ER≥2 had worse disease-free interval (DFI) and disease-specific survival (DSS) (hazard ratios (HR) = 4.96 for DFI and HR = 8.69 for DSS, bothP ≤ 0.004). According to the Prosigna-PAM50 assay, 63% (12/19) of these cases resulted in intermediate or high risk of recurrence categories. Additionally, although all samples were positive for ER assessed by IHC, the molecular test assigned 47.4% (9/19) of BCs to intrinsic non-luminal subtypes. In conclusion, the AR/ER ratio ≥2 identifies a subgroup of patients with aggressive biological features and may represent an additional independent marker of worse BC prognosis. Moreover, the Prosigna-PAM50 results indicate that a significant number of cases with AR/ER≥2 could be non-luminal tumours.

Stat5 expression predicts response to endocrine therapy and improves survival in estrogen receptor-positive breast cancer

2006 ◽  
Vol 13 (3) ◽  
pp. 885-893 ◽  
Author(s):  
H Yamashita ◽  
M Nishio ◽  
Y Ando ◽  
Z Zhang ◽  
M Hamaguchi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Epithelial Cell ◽  
Endocrine Therapy ◽  
Histological Grade ◽  
Metastatic Breast ◽  
Therapy Response ◽  
Breast Cancer Patients ◽  
Er Positive ◽  
Positive Breast Cancer

Constitutively activated signal transducers and activators of transcription (Stats), in particular Stat3 and Stat5, have been demonstrated to directly contribute to oncogenesis by stimulating cell proliferation and preventing apoptosis in various cancers. Stat3 is essential in mammary gland epithelial cell apoptosis and involution, whereas Stat5 is well established as a key factor in mammary epithelial cell growth and differentiation. Crosstalk between Stats and estrogen receptor (ER) has been demonstrated by several laboratories and we have focused on the role of Stat5 in ER-positive breast cancer. Using immunohistochemical techniques, we examined the expression of Stat3 and Stat5 in 517 human breast cancer tissues and analyzed their significance for prognosis and prediction of response to endocrine therapy. Stat5 expression was significantly correlated with histological grade (P < 0.0001), ER (P = 0.02), and progesterone receptor (P = 0.026) expression. There was no difference between Stat3 expression and clinicopathological factors. In 346 patients with ER-positive breast cancer, patients with Stat5 positive tumors had significantly increased overall survival (P = 0.0009) in multivariate analysis. There were 70 patients who received endocrine therapy as first-line treatment for metastatic breast cancer at relapse. The patients whose primary breast tumors were Stat5 positive, had significantly better response to endocrine therapy (P = 0.04), and longer survival after relapse (P = 0.0003), than those whose tumors were Stat5 negative. The present study demonstrates for the first time that Stat5 is a predictive factor for endocrine therapy response and a strong prognostic molecular marker in ER-positive breast cancer. Our data suggest that the expression of Stat5 is helpful in selecting patients who may benefit from endocrine therapy.

scholarly journals Role of carbonic anhydrase IX expression in prediction of the efficacy and outcome of primary epirubicin/tamoxifen therapy for breast cancer

2006 ◽  
Vol 13 (3) ◽  
pp. 921-930 ◽  
Author(s):  
Daniele Generali ◽  
Stephen B Fox ◽  
Alfredo Berruti ◽  
Maria P Brizzi ◽  
Leticia Campo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Carbonic Anhydrase ◽  
Cancer Patients ◽  
Tamoxifen Therapy ◽  
Carbonic Anhydrase Ix ◽  
Breast Cancer Patients ◽  
Caix Expression ◽  
Er Positive

The purpose of this study is to investigate the role of carbonic anhydrase IX (CAIX) expression in predicting the response to epirubicin and disease-free survival (DFS) in breast cancer patients enrolled in a single institution trial of primary anthracycline and tamoxifen therapy. CAIX expression was assessed in 183 patients with T2–4 N0–1 breast cancer enrolled in a randomized trial comparing four cycles of single agent epirubicin versus epirubicin + tamoxifen as primary systemic treatment. All patients received postoperatively four cycles of the four weekly i.v. cyclophosphamide, methotrexate, 5-fluorouracil regimen. Patients with estrogen receptor (ER)-positive primary tumors received 5 years of adjuvant tamoxifen. Pretreatment, p53 (P = 0.007), c-erbB2 (P < 0.01), and Ki67 (P = 0.02) were directly associated with CAIX expression, while bcl2 (P < 0.000) and ER (P = 0.000) and progesterone receptor (PgR; P < 0.01) were inversely correlated. In multivariate analysis, only high p53 and low bcl2 were independently associated with CAIX positivity. CAIX immunostaining was significantly associated with poor outcome for DFS (P < 0.002) and overall survival (P = 0.001). In multivariate analysis, a significant interaction was found between CAIX and markers of hormone sensitivity, bcl2 (P = 0.01), ER (P = 0.02), PgR (P = 0.02), and lymph node involvement (P = 0.04), in predicting DFS. Presently, there are few clinical markers of resistance to tamoxifen treatment in ER-positive tumors. CAIX expression in breast cancer patients shows a negative predictive role of treatment efficacy in ER-positive patients on the adjuvant tamoxifen after primary chemo-endocrine therapy. Studies investigating the effects of pH on tamoxifen uptake and the effects of therapy with CA inhibitors are planned.

scholarly journals A qualitative transcriptional signature to reclassify histological grade of ER-positive breast cancer patients

2019 ◽  
Author(s):  
Jing Li ◽  
Wenbin Jiang ◽  
Hailong Zheng ◽  
Jing Yang ◽  
Hao Cai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Histological Grade ◽  
Objective Assessment ◽  
Breast Cancer Patients ◽  
Transcriptional Signature ◽  
Gene Pairs ◽  
Er Positive ◽  
Positive Breast Cancer

Abstract Purpose Histological grade (HG) is commonly adopted as a prognostic factor for ER-positive breast cancer patients. However, HG evaluation methods, such as the pathological Nottingham grading system, are highly subjective with only 50%-85% inter-observer agreements. Specifically, the subjectivity in the pathological assignment of the intermediate grade (HG2) breast cancers, comprising of about half of breast cancer cases, results in uncertain disease outcomes prediction. Here, we developed a qualitative transcriptional signature, based on within-sample relative expression orderings (REOs) of gene pairs, to define HG1 and HG3 and reclassify pathologically-determined HG2 (denoted as pHG2) breast cancer patients. Results From the gene pairs with significantly stable REOs in pathologically-determined HG1 (denoted as pHG1) samples and reversely stable REOs in pathologically-determined HG3 (denoted as pHG3) samples, concordantly identified from seven datasets, we extracted a signature which could determine the HG state of samples through evaluating whether the within-sample REOs match with the patterns of the pHG1 REOs or pHG3 REOs. A sample was classified into the HG3 group if at least a half of the REOs of the 10 gene pairs signature within this sample voted for HG3; otherwise, HG1. Using four datasets including samples of early stage (I–II) ER-positive breast cancer patients who accepted surgery only, we validated that this signature was able to reclassify pHG2 patients into HG1 and HG3 groups with significantly different survival time. For the original pHG1 and pHG3 patients, the signature could also more accurately and objectively stratify them into distinct prognostic groups. And the up-regulated and down down-regulated genes in HG1 compared with HG3 involved in cell proliferation and extracellular signal transduction pathways respectively. Conclusions The transcriptional qualitative signature can provide an objective assessment of HG states of ER-positive breast cancer patients, especially for reclassifying patients with pHG2, to assist decision making on clinical therapy.

scholarly journals A qualitative transcriptional signature to reclassify histological grade of ER-positive breast cancer patients

2020 ◽  
Author(s):  
Jing Li ◽  
Wenbin Jiang ◽  
Qirui Liang ◽  
Guanghao Liu ◽  
Yupeng Dai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Histological Grade ◽  
Objective Assessment ◽  
Prognostic Significance ◽  
Breast Cancer Patients ◽  
Transcriptional Signature ◽  
Gene Pairs ◽  
Er Positive ◽  
Positive Breast Cancer

Abstract Purpose Histological grade (HG) is commonly adopted as a prognostic factor for ER-positive breast cancer patients. However, HG evaluation methods, such as the pathological Nottingham grading system, are highly subjective with only 50%-85% inter-observer agreements. Specifically, the subjectivity in the pathological assignment of the intermediate grade (HG2) breast cancers, comprising of about half of breast cancer cases, results in uncertain disease outcomes prediction. Here, we developed a qualitative transcriptional signature, based on within-sample relative expression orderings (REOs) of gene pairs, to define HG1 and HG3 and reclassify pathologically-determined HG2 (denoted as pHG2) breast cancer patients.Results From the gene pairs with significantly stable REOs in pathologically-determined HG1 (denoted as pHG1) samples and reversely stable REOs in pathologically-determined HG3 (denoted as pHG3) samples, concordantly identified from seven datasets, we extracted a signature which could determine the HG state of samples through evaluating whether the within-sample REOs match with the patterns of the pHG1 REOs or pHG3 REOs. A sample was classified into the HG3 group if at least a half of the REOs of the 10 gene pairs signature within this sample voted for HG3; otherwise, HG1. Using four datasets including samples of early stage (I–II) ER-positive breast cancer patients who accepted surgery only, we validated that this signature was able to reclassify pHG2 patients into HG1 and HG3 groups with significantly different survival time. For the original pHG1 and pHG3 patients, the signature could also more accurately and objectively stratify them into distinct prognostic groups. And the up-regulated and down down-regulated genes in HG1 compared with HG3 involved in cell proliferation and extracellular signal transduction pathways respectively. By comparing with existing signatures, 10-GPS was with prognostic significance and was more aligned with survival of patients especially for pHG2 samples.Conclusions The transcriptional qualitative signature can provide an objective assessment of HG states of ER-positive breast cancer patients, especially for reclassifying patients with pHG2, to assist decision making on clinical therapy.

Abstract P3-06-40: Prognostic impact of PgR and Ki-67 expression in ER-positive and HER2-negative breast cancer patients

2015 ◽  
Author(s):  
Yasuyuki Nishiyama ◽  
Reiki Nishimura ◽  
Tomofumi Osako ◽  
Yasuhiro Okumura ◽  
Nobuyuki Arima
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Impact ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
Er Positive

Prognostic value of gene expression of p63 by microarray analysis in estrogen receptor positive and negative breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 566-566
Author(s):  
L. C. Hanker ◽  
T. Karn ◽  
A. Rody ◽  
E. Ruckhäberle ◽  
C. Solbach ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Receptor Expression ◽  
Prognostic Impact ◽  
Breast Cancer Patients ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
Er Positive

566 Background: The protein 63 (p63) represents a member of the p53 family (p53/p63/p73) located on chromosome 3q27. This gene family seems to play an important role in carcinogenesis and its members may act as oncogenes or tumor suppressor genes. P63 is overexpressed in many different tumors like head and neck cancer, lung cancers, uterine tumors and breast cancer, and has been associated with poor prognosis in some studies. P63 was found to be overexpressed in a subset of highly aggressive breast cancers that represent a basal and myoepithelial phenotype and have a poor clinical outcome. This protein seems to be a specific myoepithelial cell marker in normal breast tissue and might represent a prognostic factor in breast cancer. Methods: Large scale analysis was performed using Affymetrix microarray data from n=1581 breast cancer patients to evaluate p63 expression. Results: P63 expression showed a strong correlation with patient's age (χ2-test, p < 0.001), tumor size (p < 0.003), proliferation rate (p < 0.001), Topo2α expression (p = 0.001) and estrogen receptor expression (p = 0.017). Survival analysis of all patients with available follow up data (n = 1263) showed a significant difference due to high and low p63 expression (log rank p < 0.001). Patients with a low p63 expression had the worst prognosis. In univariate Cox regression analysis p63 showed a hazard ratio (HR) of 1.61 (95% CI 1.31–2.00, p < 0.001) for disease free survival. This prognostic impact remained significant when samples were stratified by estrogen receptor status. High expression of p63 was significantly associated with longer OS in both ER negative (n = 334, log rank p = 0.022) and ER positive (n = 929, log rank p < 0,001) breast cancer. The prognostic impact of p63 expression was independent of Ki67 expression (p = 0.011 and p = 0.001 for high and low Ki67, respectively). Moreover a worse prognosis of low p63 expressing tumors was found in both subgroups of ErbB2 positive tumors (p < 0.001) and ErbB2 negative tumors (p < 0.001). Conclusions: P63 expression is a prognostic factor in both ER positive and negative breast cancer and could be helpful for risk assessment in breast cancer patients. No significant financial relationships to disclose.

The first report of multicenter validation study on curebest 95GC breast, a multi-gene assay to predict prognosis of node negative and ER positive breast cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12107-e12107
Author(s):  
Ken-ichi Ito ◽  
Takaaki Oba ◽  
Kenjiro Aogi ◽  
Shozo Ohsumi ◽  
Mina Takahashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Hormonal Therapy ◽  
Validation Study ◽  
Histological Grade ◽  
Breast Cancer Patients ◽  
Node Negative ◽  
Gene Assay ◽  
Er Positive ◽  
Positive Breast Cancer

e12107 Background: Curebest™ 95GC Breast (95GC) is one of the multi-gene assays to predict prognosis of node negative and estrogen receptor (ER) - positive breast cancer patients, developed using 95 gene-set without overlap with that used in Oncotype DXⓇ(ref 1). It has been shown to have the capability to classify the “intermediate” patients determined using Recurrence Online (microarray-based simulation model for Oncotype DXⓇ) but was validated only using the data from single institute and public database. Here we report the result of the first multi-center validation study for this multi-gene assay. Methods: ER-positive and T1-2/N0/M0 breast cancer patients who received adjuvant hormonal therapy were enrolled retrospectively. Fresh frozen tissues were applied to the assay, resulting classification into “L” and “H”, which was used for the validation on 5 year recurrence free survival (5Y-RFS) data of each patient. Results: 73 cases out of 150 enrolled cases were eligible and analyzed. 46 patients were classified as “L” whose 5Y-RFS was 96.5% (95%CI:89.5-98.9) while 27 patients were classified as “H” whose 5Y-RFS was 79.0% (95%CI:63.6-88.5). There was a statistically significant difference between RFS of “L” and “H” group by Log-Rank test (p = 0.0016). Significant association with 95GC were seen in histological grade (p = 0.0012), Recurrence Online (p < 0.001) and PAM50 (p < 0.001). The assay could classify the patients of histological grade 2, intermediate group by Recurrence Online (RS > 17, RS < 31) and Luminal B patients into “L” and “H”. Conclusions: Curebest™ 95GC Breast was well validated by this first multi-centered retrospective study on 5Y-RFS of the ER positive, node-negative patients who received only hormonal therapy in adjuvant setting. This result indicates the usefulness of 95GC as a novel multi-gene assay, as it can classify target patients into 2 groups, “H” and “L” according to predicted prognosis of 5Y-RFS. Reference: 1. Naoi et al. Breast Cancer Res Treat (2011) 128:632-641

Sign in / Sign up

Export Citation Format

Share Document