Autophagy-related prognostic signature in HER2 positive gastric carcinomas

2021 ◽  
Vol 21 ◽  
Author(s):  
Antonio Ieni ◽  
Cristina Pizzimenti ◽  
Giuseppe Giuffrè ◽  
Rosario Alberto Caruso ◽  
Giovanni Tuccari
Keyword(s):  
Cancer Progression ◽  
Univariate Analysis ◽  
Immunohistochemical Analysis ◽  
Beclin 1 ◽  
Clinicopathological Parameters ◽  
Her2 Status ◽  
P Value ◽  
Her2 Positive ◽  
Gastric Carcinomas ◽  
Human Pathology

Background: The immunohistochemical analysis of autophagy-related proteins (ATGs) has been recently applied in human pathology to study differentiation and cancer progression. The aim of the present study is to analyze a cohort of gastric carcinomas (GC) by five ATG antisera (Beclin-1, LC3A/B, p62, ULK-1 and AMBRA-1), also evaluating their possible relationship with clinicopathological parameters, HER2 status and final outcome of patients. Methods: A cohort of 123 GCs has been studied by ATG antisera utilizing Masuda's criteria that define positive cases in which at least two out of five protein expressions were documented. Results: The immunohistochemical signature for autophagy (A-IHC) was 49.59% as a whole. The percentage of A-IHC ranged from 31% for poorly cohesive carcinomas to 56% for adenocarcinomas. The performance of each ATG immunomarker documented high values for sensitivity, specificity and efficiency for LC3A/B, Beclin-1 and p62. In univariate analysis of GC, grade, stage, Ki67 expression, HER2 status as well as A-IHC appeared as emerged as relevant parameters with a high p-value (p < 0.001). Finally, in multivariate analysis, HER2 status, stage and A-IHC emerged as independent prognostic variables. In the comparison of survival curves, GC cases immunoreactive for A-IHC exhibited a shorter survival with a worse outcome. Conclusions: We have hypothesized that A-IHC could represent an additional morphological tool to provide prognostic elements in order to identify patients affected by aggressive with shorter survival and worse outcome.

scholarly journals Evaluation of the Relationship of PD-L1 and FOXP3 Expressions With Clinicopathological Parameters in Gastric Carcinomas

2021 ◽  
Author(s):  
Sevil Sayhan ◽  
Gülden Diniz ◽  
Duygu Ayaz ◽  
Dudu Solakoğlu Kahraman ◽  
Pınar Ayvat ◽  
...  
Keyword(s):  
Perineural Invasion ◽  
Statistical Significance ◽  
Survival Rates ◽  
Inflammatory Cells ◽  
Treg Cells ◽  
Nodal Metastasis ◽  
Clinicopathological Parameters ◽  
Survival Times ◽  
Her2 Positive ◽  
Gastric Carcinomas

Objective: At the time of diagnosis, gastric cancers are generally at an advanced stage and the survival rates are very low. The aim of this study is to determine the prognostic values of PD-L1 expression in gastric carcinomas and to detect the presence of FOXP3- positive Treg cells in tumor microenviroment. Method: In this study, PD-L1 and FOXP3 expressions were evaluated in 125 patients with gastric carcinoma who had undergone gastrectomy between 2011, and 2015. Results: The mean age of the patients was 64.18±12.3 years and the patients were followed up for a mean period of 29.6±26.4 months. In only 2 (1.6%) cases there were weak membranous expressions of PD-L1 in tumor cells. PD-L1- positive inflammatory cells were also seen in tumors of 2 (1.6%) cases. There was no significant relationship between PD-L1 expression and survival times (p= 0.690). In 57(45.6%) cases, FOXP3- positive lymphocytes were detected. The number of FOXP3-positive cells ranged between 1 and 55/HPF. There was no statistically significant correlation between the survival times and presence of Tregs (p=0.793). Twenty-two cases (17.6%) were evaluated as HER2-positive. There was a statistical relationship between HER2-positivity and perineural invasion (p=0.006). Statistical significance between survival and some prognostic factors such as nodal metastasis (p=0.004), pT stage (p<0.01) and presence of perineural invasion (p=0.010) was determined. Conclusion: This study has demonstrated that the PD-L1 positivity was not effective on gastric tumorigenesis. We have found a positive correlation between the presence of Treg inflammatory cells and PD-L1 expression. But this relationship could not be proved by statistical analyses. However since PD-L1 expression was detected in only 4 cases, these findings should be confirmed in larger series.

Comparison of Radiation With or Without Concurrent Trastuzumab for HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy: A Phase III Clinical Trial

2021 ◽  
pp. JCO.20.02824
Author(s):  
Melody A. Cobleigh ◽  
Stewart J. Anderson ◽  
Kalliopi P. Siziopikou ◽  
Douglas W. Arthur ◽  
Rachel Rabinovitch ◽  
...  
Keyword(s):  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Menopausal Status ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Her2 Status ◽  
P Value ◽  
Her2 Positive

PURPOSE Preclinical studies report that trastuzumab (T) can boost radiotherapy (RT) effectiveness. The primary aim of the B-43 trial was to assess the efficacy of RT alone vs concurrent RT plus T in preventing recurrence of ipsilateral breast cancer (IBTR) in women with ductal carcinoma in situ (DCIS). PATIENTS AND METHODS Eligibility: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, DCIS resected by lumpectomy, known estrogen receptor (ER) and/or progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status by centralized testing. Whole-breast RT was given concurrently with T. Stratification was by menopausal status, adjuvant endocrine therapy plan, and nuclear grade. Definitive intent-to-treat primary analysis was to be conducted when either 163 IBTR events occurred or all accrued patients were on study ≥ 5 years. RESULTS There were 2,014 participants who were randomly assigned. Median follow-up time as of December 31, 2019, was 79.2 months. At primary definitive analysis, 114 IBTR events occurred: RT arm, 63 and RT plus T arm, 51 (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.17; P value = .26). There were 34 who were invasive: RT arm, 18 and RT plus T arm, 20 (HR, 1.11; 95% CI, 0.59 to 2.10; P value = .71). Seventy-six were DCIS: RT arm, 45 and RT plus T arm, 31 (HR, 0.68; 95% CI, 0.43 to 1.08; P value = .11). Annual IBTR event rates were: RT arm, 0.99%/y and RT plus T arm, 0.79%/y. The study did not reach the 163 protocol-specified events, so the definitive analysis was triggered by all patients having been on study for ≥ 5 years. CONCLUSION Addition of T to RT did not achieve the objective of 36% reduction in IBTR rate but did achieve a modest but statistically nonsignificant reduction of 19%. Nonetheless, this trial had negative results. Further exploration of RT plus T is needed in HER2-positive DCIS before its routine delivery in patients with DCIS resected by lumpectomy.

Prognostic value of HER2 on breast cancer survival.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 640-640 ◽  
Author(s):  
Nora Katzorke ◽  
Brigitte Kathrin Rack ◽  
Lothar Haeberle ◽  
Julia Katharina Neugebauer ◽  
Carola Anna Melcher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Prognostic Value ◽  
Univariate Analysis ◽  
Phase Iii ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Her2 Positive ◽  
Receptor Status ◽  
Prognostic Relevance

640 Background: HER2 overexpression and overamplification have originally been described as a prognostic factor indicating a poor prognosis. However the highly effective anti-HER2 treatment was approved in 2006 after several large randomized trials showing that the prognosis in HER2 positive women could be improved. Few data has been generated comparing HER2 positive patients treated with trastuzumab with comparable HER2 negative patients. Aim of this analysis was to investigate the prognostic relevance of HER2 status in a post trastuzumab approval study. Methods: The SUCCESS trial is an open-label, multicenter, randomized controlled, phase III study comparing FEC-docetaxel (Doc) vs. FEC-Doc-gemcitabine (Doc-G) regime and 2 vs. 5 year treatment with zoledronat in 3754 patients with primary breast cancer (N+ or high risk). All patients were treated per protocol with trastuzumab, if HER2 status was shown to be positive by local pathology. Furthermore HER2 status was a stratification factor. The prognostic value of HER2 status with respect to overall survival (OS) and progression-free survival (PFS), disregarding the above stated treatment arms, was studied with Cox proportional hazards regression models in univariate as well as multivariate analyses adjusted for age, BMI, tumor size, nodal status, grading, estrogen receptor status and progesterone receptor status. Results: 2628 patients were included into this analysis. Median Follow up time was 4.8 years, 221 deaths and 412 recurrences were recorded until data base closure. HER2 was not a prognostic factor in the univariate analysis (OS: HR= 0.86, 95% CI: 0.63 to 1.19; PFS: HR = 0.95, 95% CI: 0.76 to 1.19). In the multivariate analysis all of the above stated prognostic factors were of prognostic relevance. HER2 was of prognostic relevance with a HR of 0.67 (OS, 95% CI: 0.48 to 0.92) and 0.79 (PFS, 95% CI: 0.62 to 0.99) indicating that patients with a positive HER2 status had a better prognosis. Conclusions: Patients treated with trastuzumab showed a more favourable prognosis compared to HER2 negative patients in this prospectively randomized trial, possibly due to the therapeutic effect of HER2-targeted treatment.

Androgen receptor (AR) and phospho-AR protein levels in invasive breast cancers and survival outcomes: Indication of a new prognostic marker.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 11-11
Author(s):  
Hirotaka Iwase ◽  
Takashi Takeshita ◽  
Yoko Omoto ◽  
Mutsuko Ibusuki ◽  
Yutaka Yamamoto
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Protein Expression ◽  
Prognostic Marker ◽  
Cancer Progression ◽  
Expression Patterns ◽  
Clinicopathological Parameters ◽  
Nuclear Staining ◽  
Her2 Positive ◽  
Cancer Specific Survival

11 Background: Androgen receptor (AR) in breast cancer may serve as a useful prognostic and predictive marker. We examined the expression patterns of AR and AR phosphorylated at serine-213/210 (pAR213/210) in breast cancer by immunohistochemistry, and evaluated their association with clinicopathological parameters and prognoses. Methods: The levels of AR nuclear protein expression were determined in tissue samples of 379 consecutive female patients with invasive breast cancer. In samples that showed detectable AR, the levels of pAR213/210nuclear and cytoplasmic expression were determined. All samples were scored semiquantitatively using a histoscore. Results: Nuclear staining of AR was observed in 76% of the samples. Elevated AR protein expression correlated with non-aggressive parameters and longer relapse-free survival (RFS) (p < .0001) and breast cancer-specific survival (BCSS) (p < .0001). Nuclear and cytoplasmic pAR213/210 were observed in 72.4% and 11.9%, respectively, of the tested samples. Although no statistically significant relationship between pAR213/210 nuclear expression and clinicopathological parameters was observed, increased expression of cytoplasmic pAR213/210 was associated with high nuclear grade (p = .026), estrogen receptor (ER) α-negative (p = .023), progesterone receptor (PgR)-negative (p = .034), human epidermal growth factor receptor 2 (HER2)-positive (p = .043), and Ki-67-positive (p = .026) tumors. Conversely, nuclear pAR213/210 expression correlated with longer RFS (p = .027) and BCSS (p = .0031), but cytoplasmic pAR213/210expression was not related with RFS and BCSS. Conclusions: AR and its phosphorylation at serine-213/210 are significant in breast cancer progression and prognosis. The expression levels of pAR213/210 could have potential as a new prognostic marker of breast cancer.

Exploratory analysis to investigate clinical factors that may influence trastsuzumab efficacy in patients with HER2-positive gastric cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 169-169
Author(s):  
Takeru Wakatsuki ◽  
Keisho Chin ◽  
Satoshi Matsusaka ◽  
Mariko Ogura ◽  
Masato Ozaka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Exploratory Analysis ◽  
Rank Test ◽  
P Value ◽  
Clinical Factors ◽  
Her2 Positive ◽  
Cox Regression Analysis

169 Background: ToGA study showed significant survival benefit of trastuzumab in patients with HER2 positive gastric cancer (GC); however, clinical factors which can impact its efficacy prior to treatment are still unknown. Hence, we conducted this exploratory analysis whether clinical factors could influence trastuzumab efficacy in patients with HER2 positive GC. Methods: Thirty-three HER2 positive GC patients, who were treated by trastuzumab with chemotherapy in our institute from 2011 March to 2012 December, were enrolled. Clinical factors according to ToGA study and tumor markers were examined. We retrospectively analyzed whether these clinical factors were associated with progression-free survival (PFS) and overall survival (OS). These endpoints were estimated using by Kaplan-Meier methods and compared by the log-rank test. The Cox regression analysis including only clinical factors of which p-value was less than 0.02 was done. Results: Median follow-up period was 10.8 months. Median age was 63 y.o. and 64% of the patients were male. PS 0-1, GEJ cancer, visceral metastasis (lung or liver), previous gastorectomy, previous chemotherapy, number of metastatic site (1-2), and number of metastatic lesion (1-4) were found in 97%, 27%, 58%, 36%, 21%, 76%, and 27% of the patients, respectively. Sixty-seven% and 94% of the patients were differentiated type and HER2 3+ by IHC, respectively. Baseline median CEA and CA19-9 levels were 5.2 ng/ml and 109.4 U/ml, respectively. Median PFS was 9.5 months (95% CI: 5.5-13.5) and median OS was not reached. Overall response rate by RECIST was 71.4%. Lower CA19-9 levels were associated with longer PFS in univariate analysis. Patients who had lower CA 19-9 levels showed a median PFS of 12.2 months vs. 6.9 months for patients who had higher CA19-9 levels (HR: 0.41 [95%CI: 0.17-1.00], p=0.042), however this result was not conserved in multivariate analysis. No clinical factors were associated with OS. Conclusions: Lower CA19-9 levels were associated with favorable PFS in the patients with HER2 positive GC upon when treated by trastuzunab. External clinical validations and further molecular analyses are needed to validate this result.

scholarly journals High Prevalence of Mitochondrial tRNA A3243G Mutation in Invasive Breast Cancer

2021 ◽  
Vol 6 (2) ◽  
pp. 133-139
Author(s):  
Mohammed A. Alhomidi ◽  
Qurratullain Hasan
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Invasive Breast Cancer ◽  
Cellular Proliferation ◽  
Clinicopathological Parameters ◽  
P Value ◽  
Breast Cancer Patients ◽  
Mitochondrial Trna ◽  
Cross Sectional ◽  
A3243g Mutation

Background & Aim: Mitochondria play vital roles in various cellular activities, such as energy production, maintaining the redox balance of the cell, the regulation of cellular proliferation and differentiation, and programmed cell death. Mitochondrial tRNA mutations are associated with many pathological conditions and numerous diseases have been associated with them. Therefore, the objectives of this study were to evaluate the presence and the frequency of mutations in the selected tRNAs in breast cancer patients and to correlate these mutations with the clinicopathological characters. Materials & Methods: The is a cross sectional study, where seventy seven breast tumors and adjacent non-tumorous (normal) tissue samples were analyzed by PCR- RFLP, and direct DNA sequencing. In this study three mt-tRNAs wre selected, two of them are the most important disease associated mt-tRNAs i.e tRNALue (UUR), tRNALys and one of the least pathogenic associated tRNA which is tRNAarg. Statistical analysis was used to determine the relationship between the detected mutations and the clinicopathologhical characters. Results: The tRNAleu (UUR) A3243G mutation occurring at the highly conserved location was detected in 4 samples (5.2%) of both breast cancer and adjacent non-tumorous tissue except one detected only in tumor tissue. Another A8343G mutation was detected in tRNAlys. There was no significant association between these mutations and clinicopathological parameters (P. value > 0.05). Conclusion: The detection of high frequent A3243G mutations in patients with invasive breast cancer suggests role of this mutation in the carcinogenesis. This mutation affects complex I, reduces translation of its core subunits, which can contribute to the impairment of oxidative phosphorylation and increase ROS production, leading to cancer progression.

scholarly journals Immunohistochemical Expression of Autophagy-Related Proteins in Advanced Tubular Gastric Adenocarcinomas and Its Implications

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 389 ◽  
Author(s):  
Antonio Ieni ◽  
Roberta Cardia ◽  
Giuseppe Giuffrè ◽  
Luciana Rigoli ◽  
Rosario Alberto Caruso ◽  
...  
Keyword(s):  
High Efficiency ◽  
Univariate Analysis ◽  
Beclin 1 ◽  
Clinicopathological Parameters ◽  
Tubular Adenocarcinoma ◽  
Low Grade ◽  
High Grade ◽  
Ki 67 ◽  
Gastric Adenocarcinomas ◽  
Related Proteins

In neoplastic conditions, autophagy may act as a tumor suppressor avoiding the accumulation of damaged proteins and organelles or as a mechanism of cell survival promoting the tumor growth. Although ultrastructural analysis has been considered the traditional method to identify autophagy, some proteins such as microtubule-associated protein 1 light chain 3 (LC3A/B), Beclin-1 and activating molecule in Beclin-1-regulated autophagy protein-1 (AMBRA-1) may be considered as markers of autophagy-assisted cancerogenesis. Herein, we analyzed a cohort of advanced tubular gastric adenocarcinomas by the abovementioned immunohistochemical antisera; through immunohistochemistry, autophagy (A-IHC) is diagnosed when at least two out of the three proteins are positive in the samples. Immunostaining for LC3A/B, Beclin-1, and AMBRA-1 was exclusively found in neoplastic elements, but not in surrounding stromal cells. In detail, LC3A/B and Beclin 1 were expressed both in the cytoplasm and in the nucleus of the cancer cells, while AMBRA-1 was preferentially localized in the nucleus, mainly in high grade cases. LC3A/B, Beclin 1, and AMBRA-1 expression were positive in 18 (56.2%), 17 (53.1%), and 12 (37.5%) cases, respectively. The sensibility and specificity of LC3A/B and Beclin-1 ranged from 81.25% to 93.75%, with high efficiency (90.63%) for Beclin-1. Moreover, the ultrastructural autophagic index (AI) was also available in all cases. All high-grade cases documented a Ki-67 labelling index (LI) ≥ 30%, even if three low-grade cases revealed a high Ki-67 value; p53 positivity was encountered in 21/32 (65.62%) of cases, independently of the tumor grade. A statistically significant correlation among A-IHC and clinicopathological parameters such as grade, stage, clinical course, Ki-67 LI and AI was revealed. Univariate analysis documented a significant p-value for the same autophagic variables. Additionally, multivariate survival analysis identified the grade, AI and A-IHC as independent significant variables. Finally, the overall survival curves of all cases of gastric tubular adenocarcinoma were greatly dependent on A-IHC. Therefore, we suggest that autophagic-related proteins might be considered promising predictive prognostic factors of advanced gastric cancer. Further investigations may be required to determine whether new targeted therapies should be addressed to autophagy-related proteins.

scholarly journals The IMMUNOHISTOCHEMICAL EXPRESSION OF NOVEL B7-H6 IN ORAL SQUAMOUS CELL CARCINOMA AND CORRELATION WITH HISTOLOGICAL DIFFERENTIATION AND CLINICOPATHOLOGICAL PARAMETERS

2019 ◽  
Vol 3 (11) ◽  
Author(s):  
Taqia Fauzia ◽  
Serajuddaula Syed ◽  
Faraz Ahmed Baig ◽  
Maheen Zakaria
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Histological Grade ◽  
Immunohistochemical Analysis ◽  
Clinicopathological Characteristics ◽  
Clinicopathological Parameters ◽  
P Value ◽  
Immunohistochemical Expression

B7-H6 is a new immune checkpoint molecule related to B7 family; however, little research has been performed to determine its expression among tumors. In this study, we investigated the immunohistochemical expression of B7-H6 protein in 141 biopsy proven oral squamous cell carcinoma tissues. The specimens were subjected for immunohistochemical analysis to evaluated B7-H6 expression and was graded according to the intensity of cytoplasm and membrane staining. The distribution of B7-H6 expression was also correlated with different clinicopathological parameters of oral squamous cell carcinoma.Overall, 69 out of 141 oral squamous cell carcinoma cases had shown the expression of B7-H6 protein, majority of which belongs to moderately differentiated histological grade. This accounts for strong statistical association of B7-H6 with oral squamous cell carcinoma (P-value=0.001). The distribution of B7-H6 was also observed across broad range of clinicopathological characteristics of disease, however only long term naswar consumers have shown significant statistical difference with B7-H6 expression. We thus conclude that, B7-H6 may represent a new marker for oral squamous cell carcinoma with potential to forecast biological aggressiveness of oral squamous cell carcinoma. Hence, B7-H6 may serve as an immune target for oral squamous cell carcinoma therapy, which needs to evaluated in future studies.

HUBUNGAN LAMA WAKTU MENDERITA STROKE DENGAN TINGKAT KEMANDIRIAN KLIEN DALAM MELAKUKAN AKTIVITAS PEMENUHAN KEBUTUHAN SEHARI-HARI

2018 ◽  
Vol 1 (2) ◽  
pp. 58
Author(s):  
Setia Budi ◽  
Ria Dila Syahfitri
Keyword(s):  
Data Analysis ◽  
Univariate Analysis ◽  
Sampling Technique ◽  
P Value ◽  
Cross Sectional ◽  
Stroke Incidence ◽  
Bivariate Data ◽  
Cross Sectional Design ◽  
Interviewing Techniques ◽  
Need For Rehabilitation

The rate of stroke incidence is about 200 per 100,000 people throughout the world. This study aims to determine the Relation Suffer Stroke With Independence Level In Neurology Polyclinic TK II DR Ak Gani Palembang Year Hospital 2017. The research method used is descriptive quantitative with cross sectional design that is done by interviewing techniques with questionnaires on 42 respondents with Accidental sampling technique. This research was conducted in August 2017. Data analysis used is univariate data analysis and bivariate data analysis with one way anova test result. The results of univariate analysis showed that the duration of the respondents suffering from stroke was between 2.10 years to 3.38 years. Also found that most respondents were at the level of independence f; independent, except bathing, dressing, moving, and one other function with a total of 12 respondents. The results showed that there was a significant relationship between the long suffering stroke with the level of independence with the value of p value 0.025. For that the need for rehabilitation to patients and families of patients in order to help improve the independence of stroke patients in doing their daily activities. Keywords : Long Suffer Stroke, Level of Independence

Co-expression of ER-beta and HER2 associated with poorer prognosis in primary breast cancer

2009 ◽  
Vol 32 (3) ◽  
pp. 250 ◽  
Author(s):  
Wen-sheng Qui ◽  
Lu Yue ◽  
Ai-ping Ding ◽  
Jian Sun ◽  
Yang Yao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Differentiation ◽  
Primary Breast Cancer ◽  
Tumour Size ◽  
Univariate Analysis ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Er Alpha

Purpose: To assess the prognostic value of co-expression of estrogen receptor (ER)-beta and human epidermal growth factor receptor 2 (HER2) in primary breast cancer patients in China. Methods: Tumour specimens from 308 patients undergoing surgery for primary breast cancer were evaluated. Expression of ER-beta and HER-2 was investigated by the immunohistochemistry. Results: 123 patients (40%) were ER-beta positive and 58 (18.5 %) were HER2 positive. Among the 58 HER2 positive patients, 44 were ER-beta positive and 14 were ER-beta negative. ER-beta positive was associated with HER2 positive (75.9%, P=0.018) as well as ER-alpha positive (79.7%, P=0.023), poor cell differentiation (77.2% grade 2 or 3, P=0.010) and menopause age < 45 yr (55.3%, P=0.031). HER2 positive was associated with poor cell differentiation (93.1%, P=0.001), ?3cm tumour size (67.2%, P=0.011). Conclusion: Both ER-beta positive and HER2 positive status was associated with poorer overall survival (OS) by univariate analysis. In both HER2 positive and HER2 negative subgroups, ER-beta positive was associated with poorer distant disease free survival (DDFS) but not OS, which implied that ER-beta might relate to metastasis in breast cancer.

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