scholarly journals 8p11.23 Amplification in Breast Cancer: Molecular Characteristics, Prognosis and Targeted Therapy

2020 ◽  
Vol 9 (10) ◽  
pp. 3079 ◽  
Author(s):  
Ioannis A. Voutsadakis
Keyword(s):  
Breast Cancer ◽  
Transcription Initiation ◽  
Zinc Finger Protein ◽  
Growth Factor Receptor ◽  
Initiation Factor ◽  
Molecular Characteristics ◽  
Breast Cancers ◽  
Free Survival ◽  
Luminal B ◽  
Over Expression

Background: Amplification of the locus 8p11.23 has been observed in cancer and genes of this locus, including ZNF703 (Zinc finger protein 703), NSD3 (Nuclear receptor binding SET domain protein 3) and FGFR1 (Fibroblast growth factor receptor 1), have been put forward as dominant oncogenes conferring pathophysiologic benefit in cancers with amplifications. However, there is no consensus on the importance of each of them or any other genes of the amplicon or even a consensus on which genes are part of the amplicon. Methods: Publicly available data were used to characterize the locus amplified at 8p11.23 and derive information on each of the genes and roles as oncogenes. The frequency of the amplifications in the locus was examined in the cBioportal platform, and expression levels of the amplicon genes in amplified cases were derived from genomic studies reported in the platform. Examination of the influence of mRNA expressions of each gene of the locus for Recurrence-free survival in breast cancer was performed using K-M plotter. Results: The 8p11.23 amplicon is present in higher frequency in squamous cell lung carcinomas, breast cancers and bladder carcinomas and is only rarely observed in other cancers. The most frequently amplified genes within the amplicon vary between different types of cancers. In breast cancer, amplified cases are most commonly of the luminal B type. Amplified genes are not always over-expressed and there is a low correlation of amplification with over-expression in amplicon genes with variation between genes. The presence of the amplicon does not influence the aneuploidy score or the tumor mutation burden of breast cancers. Regarding prognosis, the two genes of the amplicon whose mRNA hyper-expression portends adverse relapse-free survival in breast cancer are EIF4EBP1 (Eukaryotic transcription initiation factor 4E binding protein 1) and LSM1 (LSM1 homolog, mRNA degradation associated). Conclusion: Besides the previously proposed genes to play a role as dominant oncogenes in the 8p11.23 cancer amplified locus, other genes may also be important in breast cancer based on the high correlation of their amplification and mRNA expression and adverse prognosis conferred by over-expression, consistent with an oncogenic role.

GRB7 and HER2 protein overexpression and breast cancer outcome

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11102-11102
Author(s):  
S. Luoh ◽  
E. E. Ramsey ◽  
T. Bai ◽  
E. J. Keenan
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Gene Amplification ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Axillary Lymph ◽  
P Values ◽  
Free Survival ◽  
Her2 Protein ◽  
Over Expression

11102 Background: The growth factor receptor-bound protein-7 gene (GRB7) encodes a multi-domain signal transduction molecule and is located in close proximity to human epidermal growth factor receptor 2 (HER2) on chromosome 17q11–12. This study examines the roles of GRB7 protein in human breast cancer. Methods: We performed western blotting analysis of protein extracts from 563 annotated frozen breast tumors, collected from 1988 - 1998. GRB7 and HER2 bands were assigned low or high values compared to specific protein controls, and tubulin bands. Chi-square tests were used to test the hypothesis that there was no association between expression status of GRB7 or HER2 with clinical covariates and outcomes. Univariate Cox regression was performed to identify risk factors and Cox proportional hazards backward step model for variable selection to identify independent predictors of progression free survival. All P values were two sided. P values less than 0.05 were considered statistically significant. HER 2 gene amplification status was determined by fluorescence in situ hybridization (FISH). Results: GRB7 protein over-expression was associated with negative estrogen (< 5 fmole/mg protein) and progesterone receptor (< 10fmole/mg protein) status, higher grade (1, 2, or 3), larger primary tumor size (< 2.0 vs. > 2.0 cm), (more) axillary lymph node involvement (continuous), higher clinical stage (1, 2, 3, or 4) and shortened progression free survival (months). We found a discrepancy in HER2 and GRB7 protein over-expression. Isolated GRB7 protein over-expression correlated with inferior progression free survival, while HER2 protein over-expression without GRB7 protein over-expression did not. Multivariate analysis revealed that GRB7 over-expression was an independent predictor of progression free survival (hazard ratio 1.69: 95% confidence interval, 1.073 - 2.672; P = 0.0236). All 18 tumors submitted to FISH analysis that over-expressed both HER2 and GRB7 proteins and no tumors (0 / 10) with HER2 but no GRB7 protein over-expression demonstrated HER2 gene amplification. Conclusions: GRB7 protein over-expression is an independent adverse prognostic factor in breast cancer. No significant financial relationships to disclose.

scholarly journals ER, PR, HER2, Ki-67 and CK5 in Early and Late Relapsing Breast Cancer—Reduced CK5 Expression in Metastases

2013 ◽  
Vol 7 ◽  
pp. BCBCR.S10701 ◽  
Author(s):  
Kristiina Joensuu ◽  
Marjut Leidenius ◽  
Mia Kero ◽  
Leif C. Andersson ◽  
Kathryn B. Horwitz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Triple Negative ◽  
Significant Risk ◽  
Growth Factor Receptor ◽  
Primary Therapy ◽  
Breast Cancers ◽  
Luminal A ◽  
Ki 67 ◽  
Luminal B

Breast cancer can recur even decades after the primary therapy. Markers are needed to predict cancer progression and the risk of late recurrence. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), proliferation marker Ki-67, and cytokeratin CK5 were studied to find out whether their expression or occurrence in subgroups of breast cancers correlated with the time of recurrence. The expression of HER2, ER, PR, Ki-67, and CK5 was studied by IHC in 72 primary breast cancers and their corresponding recurrent/metastatic lesions. The patients were divided into three groups according to the time of the recurrence/metastasis: before two years, after 5 years, and after 10 years. Based on their IHC profiles, the tumors were divided into surrogates of the genetically defined subgroups of breast cancers and the subtype definitions were as follows: luminal A (ER or PR+HER2–), luminal B (ER or PR+HER2+), HER2 overexpressing (ER–PR–HER2+), triple-negative (ER–PR–HER2–), basal-like (ER–PR–HER2–CK5+), non-classified (ER–PR–HER2–CK5–) and luminobasal (ER or PR+CK5+). In multivariate analysis, tumor size and HER2 positivity were a significant risk of early cancer relapse. The metastases showed a significantly lower CK5 expression. CK5 positivity distinguished triple negative tumors into rapidly and slowly recurring cancers. The IHC subtype ER or PR+HER2– luminal A presented a significantly lower risk of early tumor recurrence. Ki-67 expression denoted early-relapsing tumors and correlated linearly with tumor progression, since Ki-67 positivity declined gradually from early-relapsing toward late-recurring cancers.

scholarly journals Characterizing the Relapse Potential in Different Luminal Subtypes of Breast Cancers with Functional Proteomics

2020 ◽  
Vol 21 (17) ◽  
pp. 6077
Author(s):  
Tung-Yi Lin ◽  
Pei-Wen Wang ◽  
Chun-Hsun Huang ◽  
Pei-Ming Yang ◽  
Tai-Long Pan
Keyword(s):  
Breast Cancer ◽  
Cathepsin D ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Term Survival ◽  
Luminal B ◽  
Functional Roles ◽  
The Matrix

Poor prognosis due to the high relapse and metastasis rates of breast cancer has been particularly linked to the luminal B subtype. The current study utilized MCF-7 and ZR-75-1 to investigate various luminal subtypes of breast cancers that have discrepant expressions in the estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). Understanding of the differential protein profiles and the associated pathways could help alleviate the malignance and promote the long-term survival rate of breast cancer patients. Functional proteome tools were applied to comprehensively delineate the global protein alterations that reflect the varieties of biological features between the two subtypes. In this study, a total of 11 proteins with significant and meaningful changes were identified. These protein targets including PRX2, CK19, nucleophosmin and cathepsin D were mostly involved in cell differentiation or proliferation. Particularly, cathepsin D was highly expressed in the luminal B subtype. Moreover, the level of cathepsin-D was also upregulated in the clinical metastatic tissues. Accordingly, the RNA interference-mediated silencing of cathepsin D stimulated ER expression but suppressed the level of HER2. The knockdown of cathepsin D enhanced the level of ZO-1 and a remarkable decrease in N-cadherin was also detected. Again, the matrix metalloproteinases (MMP) activity was impaired under the cathepsin D abolishment. Collectively, this study represented a modality to explore novel relationships in a proteome complex and highlighted the functional roles of cathepsin D in treatment options for different subtypes of breast cancer.

scholarly journals Testing for HER2 in Breast Cancer: A Continuing Evolution

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Sejal Shah ◽  
Beiyun Chen
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Free Survival ◽  
Humanized Monoclonal Antibody ◽  
Epidermal Growth ◽  
Invasive Breast Carcinomas ◽  
Disease Free

Human epidermal growth factor receptor 2 (HER2) is an important prognostic and predictive factor in breast cancer. HER2 is overexpressed in approximately 15%–20% of invasive breast carcinomas and is associated with earlier recurrence, shortened disease free survival, and poor prognosis. Trastuzumab (Herceptin) a “humanized” monoclonal antibody targets the extracellular domain of HER2 and is widely used in the management of HER2 positive breast cancers. Accurate assessment of HER2 is thus critical in the management of breast cancer. The aim of this paper is to present a comprehensive review of HER2 with reference to its discovery and biology, clinical significance, prognostic value, targeted therapy, current and new testing modalities, and the interpretation guidelines and pitfalls.

scholarly journals High Risk of Recurrence for Patients With Breast Cancer Who Have Human Epidermal Growth Factor Receptor 2–Positive, Node-Negative Tumors 1 cm or Smaller

2009 ◽  
Vol 27 (34) ◽  
pp. 5700-5706 ◽  
Author(s):  
Ana M. Gonzalez-Angulo ◽  
Jennifer K. Litton ◽  
Kristine R. Broglio ◽  
Funda Meric-Bernstam ◽  
Ronjay Rakkhit ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Distant Recurrence ◽  
Recurrence Free Survival ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Free Survival ◽  
Node Negative ◽  
Epidermal Growth

Purpose To evaluate the risk of recurrence in women diagnosed with T1a and T1b, node-negative, human epidermal growth factor receptor 2 (HER2) –positive breast cancer. Methods We reviewed 965 T1a,bN0M0 breast cancers diagnosed at our institution between 1990 and 2002. Dedicated breast pathologists confirmed HER2 positivity if 3+ by immunohistochemistry or if it had a ratio of 2.0 or greater by fluorescence in situ hybridization (FISH). Patients who received adjuvant chemotherapy or trastuzumab were excluded. Kaplan-Meier product was used to calculate recurrence-free survival (RFS) and distant recurrence–free survival (DRFS). Cox proportional hazard models were fit to determine associations between HER2 status and survival after adjustment for patient and disease characteristics. Additionally, 350 breast cancers from two other institutions were used for validation. Results Ten percent of patients had HER2-positive tumors. At a median follow-up of 74 months, there were 72 recurrences. The 5-year RFS rates were 77.1% and 93.7% in patients with HER2-positive and HER2-negative tumors, respectively (P < .001). The 5-year DRFS rates were 86.4% and 97.2% in patients with HER2-positive and HER2-negative tumors, respectively (P < .001). In multivariate analysis, patients with HER2-positive tumors had higher risks of recurrence (hazard ratio [HR], 2.68; 95% CI, 1.44 to 5.0; P = .002) and distant recurrence (HR, 5.3; 95% CI, 2.23 to 12.62; P < .001) than those with HER2-negative tumors. Patients with HER2-positive tumors had 5.09 times (95% CI, 2.56 to 10.14; P < .0001) the rate of recurrences and 7.81 times (95% CI, 3.17 to 19.22; P < .0001) the rate of distant recurrences at 5 years compared with patients who had hormone receptor–positive tumors. Conclusion Patients with HER2-positive T1abN0M0 tumors have a significant risk of relapse and should be considered for systemic, anti-HER2, adjuvant therapy.

scholarly journals Breast Cancer Molecular Subtypes Among Moroccan Women

2016 ◽  
Vol 3 (2) ◽  
pp. 47-54
Author(s):  
Wissal Mahir ◽  
Lamiaa Rouas ◽  
Driss Ferhati ◽  
Brahim Rhrab ◽  
Zaitouna Alhamany ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
Genomic Analysis ◽  
Molecular Profile ◽  
Molecular Heterogeneity ◽  
Breast Cancers ◽  
Luminal A ◽  
Tissue Samples ◽  
Luminal B ◽  
Molecular Group

Introduction: Breast cancer remains despite the therapeutic progress, the leading cause of death by cancer among women. It represents a group of very heterogeneous clinical, histopathological and molecular diseases. Molecular heterogeneity has been demonstrated by genomic analysis, even for similar histology cancers. Four subgroups of breast carcinomas are distinguished: Luminal A, Luminal B, HER2 over expression and Basal - like. The Immuno-histo-chemical analysis useip (estrogen receptors) RE, the PR (progesterone receptors), the ((Human Epidermal Growth Factor Receptor-2), the Ki67 (proliferation marker) HER2, CK5/6) has shown a subdivision into subgroups similar to those found by genomic analysis. These subgroups are different from the point of view of clinical course and response to adjuvant treatment. Objectives: The aim of this work is to study the molecular profile of the breast cancers by immunostaining on Moroccan series to a classification with a prognostic value allowing a treatment tailored to each group of patients. Furthermore, the molecular subgroups were correlated to other clinical and histological factors. Material and methods: It is a prospective study of the laboratory of Anatomy and Pathologic cytology of the children's Hospital, the service I of the maternity hospital in Rabat and in cooperation with the United Nations Centre of pathological anatomy. To do this, 88 cases of breast cancer together were diagnosed between January 1, 2010 and December 31, 2014, taking a period of five years. All tissue samples made subject study of Immuno-histo-chemistry with the following markers: RE, PR, HER2 and Ki67. Only negative triple cases (HR and HER2 negative) benefited from an additional marking with CK5/6 and EGFR to set the basal profile. Results: Series of 88 cases of mammary carcinomas observed on operating parts, ranged in age between 28 and 84 years old, with an average of 51 ± 12, 8. Carcinoma infiltrating non-specific (DOCTORS) was the most frequent (87.5%). Ranks histo-prognostic Scarff Bloom and Richardson (SBR) 2 and 3 respectively accounted for 45.5 and 51.1% of cases and only 2, 3% of the DOCTORS were grade 1. The Luminal B (53.4%) was under the most common molecular group, followed by Luminal A (23.9%), HER2 + (15.9%) and triple negative (6.8%). The correlation of molecular type of tumors with different prognostic factors showed only one significant connection with the SBR grade.

scholarly journals Subtypes of Breast Cancer in Northern India- An Immunohistomolecular Subtypes of Invasive Breast Cancer

2020 ◽  
Author(s):  
Amit Kumar Sinha ◽  
Amrita Ghosh
Keyword(s):  
Breast Cancer ◽  
Therapeutic Response ◽  
Molecular Subtype ◽  
Growth Factor Receptor ◽  
Normal Breast ◽  
Breast Cancers ◽  
Luminal A ◽  
Luminal B ◽  
Molecular Subclass ◽  
Epidermal Growth

Introduction: Breast cancer is a heterogeneous disease that may differ in therapeutic response and prognosis despite similarities in histopathologic types, grade and stage. Molecular studies have identified distinct subtypes of breast carcinoma each having unique recognisable phenotypes and clinical outcomes. Aim: To study the histomorphological features and Immunohistochemical (IHC) profile of breast cancer, to study the distribution of molecular subclass, and to study the morphological features of different molecular subclasses and to determine the association between the pathological features associated with adverse prognosis with the molecular subclass. Materials and Methods: Present study was a prospective cross-sectional observational study based on mastectomy specimens of 122 cases of consecutive cases of invasive breast cancer submitted from June 2012 to February 2014 in Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India. On IHC staining with Estrogen Receptors (ER), Progesterone Receptors (PR), Human Epidermal growth factor Receptor 2 (HER2), Cytokeratin (CK5/6) and Epidermal Growth Factor Receptor (EGFR) these cases were classified into Luminal A, Luminal B, HER2 overexpression, basal like and normal breast like molecular subclass. All statistical analysis were performed using Statistical Package for the Social Sciences (SPSS) version 16 (SPSS, Inc., Chicago, IL, USA). Results: The proportion of each subytpes detected in present study were: Luminal A-28.69% (35), Luminal B-17.21% (21), HER2 over expressing-25.41% (31), Basal Like Breast Carcinoma (BLBC)-26.23% (32) and the rest unclassified category (normal breast like)-2.46% (3). The following variables were significantly associated with molecular breast cancer subtypes. The tumours of BLBC and HER2 overexpressing were larger, poorly differentiated, higher mitotic index, more number of positive lymph nodes and with more geographic and central necrosis than Luminal A group. These features were statistically significant (p<0.05). Conclusion: Identification of molecular subtype of breast cancer is extremely important for predicting prognosis and therapeutic response of the breast cancers and thus has role in management of patients of breast cancers. BLBC is a molecular subtype of breast cancer known for its aggressive behaviour and poor prognosis is identified by expression of basal CKs.

Results of a fifty-gene breast cancer RNA subtype classifier applied to 167 colorectal cancer (CRC) patients.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 20-20
Author(s):  
Sandeep K. Reddy ◽  
Tara Elisabeth Seery ◽  
Christopher Szeto
Keyword(s):  
Breast Cancer ◽  
Molecular Subtype ◽  
Published Data ◽  
Breast Cancers ◽  
Rna Seq ◽  
Luminal A ◽  
Luminal B ◽  
Over Expression ◽  
Whole Exome ◽  
Transcriptomic Sequencing

20 Background: ERBB2 (HER2) is thought to be a target in <10% of CRC patients versus 20% of breast cancers, 15% of gastroesophageal cancers, and 10% of biliary cancers, based on FISH or IHC. Intrinsic molecular subtype is used to classify cancers into distinct biologic subtypes (eg. CMS 1-4 in CRC). A 50-gene qPCR assay (PAM50) identifies 5 intrinsic biological subtypes: luminal A, luminal B, HER2-enriched, basal-like, and normal-like in breast cancer. The HERACLES trial (trastuzumab plus lapatinib) resulted a 32% ORR and median TTP of 5.5 months in heavily pre-pretreated HER2+ CRC patients. We determined molecular subtypes using the 50-gene breast cancer classifier to identify an expanded CRC patient population eligible for HER2 therapy. Methods: Retrospective analysis on Whole exome (WES) DNA tumor and paired germline and matched deep whole transcriptomic sequencing (RNA-Seq) (∼200x106 reads per tumor) data from NantHealth was performed. Breast Cancer Intrinsic Subtypes based on RNAseq was used to classify CRC into 5 BC subtypes. Results: 167 CRC patients were classified using the Nant50 Breast Cancer classifier: 15.0% as Luminal B, 13.1% as Luminal A, and 1.8% as Basal-like. Surprisingly, 117/167 (70%) classified as HER2-enriched (HER-E). 15/167 (9.0%) had over-expression of ERBB2 by RNAseq or CN gain, which is consistent with published data of HER2+ CRC. ERBB2 is very significantly differentially expressed in HER2-E subtyped CRC (p=<0.001), more than ERBB2 CN gain, suggesting that HER2-E may be more HER2 driven. Across subtypes APC and TP53 were the most commonly mutated genes at 65.3% and 52.6% respectively, however both were more enriched in HER2-E CRC (APC OR=3.3, p=0.001, TP53 OR=2.6, p=0.007). Other known drivers of CRC such as PIK3CA, KRAS, and BRAF, were not differentially mutated in HER2-E CRC, however NRAS mutants were significantly more enriched in non-HER2-E CRC (OR=4.6, p=0.02). Conclusions: Even after excluding known HER2 over-expression and CN gain, PAM50-like gene classifier identifies a far higher than expected percentage of HER-E subtype CRC (99/167 = 59%) which may represent an under appreciated population for HER2 directed therapy and clinical trials.

Luminal B Breast Cancer: Molecular Characterization, Clinical Management, and Future Perspectives

2014 ◽  
Vol 32 (25) ◽  
pp. 2794-2803 ◽  
Author(s):  
Felipe Ades ◽  
Dimitrios Zardavas ◽  
Ivana Bozovic-Spasojevic ◽  
Lina Pugliano ◽  
Debora Fumagalli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Characterization ◽  
Hormone Receptors ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Luminal A ◽  
Proliferation Markers ◽  
Ongoing Research ◽  
Next Generation Sequencing Technology ◽  
Luminal B

Gene expression profiling has reshaped our understanding of breast cancer by defining and characterizing four main intrinsic molecular subtypes: human epidermal growth factor receptor 2–enriched, basal-like, luminal A, and luminal B subtypes. Luminal B breast cancer has been reported to have lower expression of hormone receptors, higher expression of proliferation markers, and higher histologic grade than luminal A. It also exhibits worse prognosis and has a distinct profile of response to hormone therapy and chemotherapy. Although luminal cancers share similarities, the studies conducted in recent years using next-generation sequencing technology show that luminal A and B breast cancers should be perceived as distinct entities, with specific oncogenic drivers, rather than more proliferative varieties of luminal tumors. This review discusses the definition and molecular characterization of luminal B breast cancer and presents the available clinical evidence for chemotherapy and endocrine therapy patterns of response. It also provides an overview of ongoing research on molecularly targeted agents for this disease.

Use of microarray analysis of differentially expressed genes in luminal B subtype of breast cancers to evaluate NHERF1 as a marker of endocrine resistance

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11015-11015
Author(s):  
A. Rody ◽  
T. Karn ◽  
C. Solbach ◽  
E. Ruckhaeberle ◽  
L. Hanker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Biology ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Endocrine Treatment ◽  
Breast Cancers ◽  
Free Survival ◽  
Luminal B ◽  
Disease Free

11015 Background: In vitro and in vivo data demonstrate that the expression of estrogen receptor (ER) in breast cancer is mainly associated with low proliferation. Gene expression profiling has recently been used to identify a group of high proliferating estrogen receptor positive breast cancers (the luminal B subtype), which are associated with a prognosis that is even worse than that of high proliferating estrogen receptor negative tumors. The analysis of those tumors might provide valuable information about breast cancer biology and could be helpful for adjuvant or neoadjuvant treatment decisions.Methods and Results: We analyzed microarray data from breast cancer specimens to gain insight into genes which play a role in estrogen receptor signalling. Genes were identified showing strong expression in high proliferating ER-positive tumors but no expression in either Ki67-/ER+ or Ki67+/ER- samples. Among these genes the Na+/H+ exchanger regulatory factor NHERF1 was found. We assessed the clinical relevance of NHERF1 transcript levels using a total of 2469 breast cancers. Analysis indicates that enhanced NHERF1 expression is associated with metastatic progression and poor prognosis of breast cancer patients. We found no correlation between NHERF1 and the nodal status as well as age, but positive correlations for tumor size (P<0.001), grade (P<0.001) and erbb2 (P=0.033). Weak NHERF1 expression correlated with longer disease free survival (DFS) in grade 1 and 2 tumors, but not in grade 3 breast cancers. Since NHERF1 expression is strongly linked to the presence of ER, the predictive value for endocrine treatment was analyzed. For samples with weak or none NHERF1 expression a treatment benefit was observed (P=0.007). While untreated patients display a 10 yr DFS rate of 67.2 ± 3.8%, endocrine treatment resulted in 80.1 ± 4.0%. In contrast no differences in disease free survival were found for corresponding NHERF1 expressing breast cancers. Conclusions: Our data indicate that expression of NHERF1 defines a state of differentiation, where breast cancer cells are refractory to endocrine treatment. No significant financial relationships to disclose.

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