Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant breast tumors display a wide variety of clinical and pathological features. The rapid development of molecular technologies over the last decade, using micro-array and expression studies to assess human diseases, has revolutionized the field of breast cancer characterization. The technique is based on simultaneous assessment of thousands of genes used to define the metabolic status of tumor cells and their active interaction with the microenvironment. Using hierarchal clustering to profile tumors according to expression of intrinsic genes, locally advanced breast cancers were classified into several major sub-groups, including: 1. Luminal-epithelial group (with sub-classification into types A and B), characterized by expression of the estrogen receptor and genes associated with the estrogenic function; 2. Basal-epithelial group, typically negative for the estrogen and progesterone receptors and the Her2/neu oncogene; 3. ERBB2+ group associated with over expression of the Her2 amplicone; 4. Normal breast-like group. Those sub-groups are the results of different pathophysiological processes, and their clinical outcomes are unique and predictable. Using supervised analysis, in which clinical outcome is pre-defined, several "poor prognostic expression signatures" were found to be associated with an increased risk of relapse, including: a 70-gene cluster in young patients with node-negative tumors, expression signature characteristic of the wound-response activity in node-positive and/or negative tumors, and the Oncotype DX system relevant for risk stratification and systemic treatment recommendations in node-negative receptor-positive tumors. Benefits and limitations of those methods and future directions are discussed.
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PMID:[Molecular portrait of breast cancer with sub-classification of breast tumor]. 1729 49

Bone is one of the most common sites of distant metastasis for breast carcinomas. In this study, our objective is to identify molecular markers and molecular subtypes that may predict patients at higher risk of developing bone metastasis. Immunohistochemical analysis with antibodies against estrogen receptor alpha, progesterone receptor, androgen receptor, Her2/neu, epidermal growth factor receptor, CK5/6, CK14, CK17, CK8, and CK18 was performed on representative sections of 21 breast carcinomas with bone metastasis and 94 cases without bone metastasis. The expression rates of receptors, subtype distributions (basal versus nonbasal) of 3 molecular classifications (cytokeratin, triple negative, and cytokeratin/triple negative), and 5 subtypes of cytokeratin/triple negative classification were compared between these 2 groups. We found that (1) the breast cancers with bone metastasis were associated with a significant percentage of estrogen receptor-positive/progesterone receptor-negative tumors compared with tumors without bone metastasis (38% versus 6%, P < .0001). (2) There was significant difference on estrogen receptor expression between high grade and non-high grade in tumors with or without bone metastasis (P = .0084 and 1.0000, respectively). (3) The breast cancers with bone metastasis were more likely to be estrogen receptor positive (85%) and androgen receptor positive (95%) compared with those without bone metastasis (59% and 74%, respectively, both P < .05). (4) There was no significant difference between tumors with or without bone metastasis in subtype distribution (basal versus nonbasal) among all 3 molecular classifications. (5) Luminal B carcinomas of cytokeratin/triple negative classification tended to be associated with bone metastasis but not to a statistically significant extent. In conclusion, bone metastasis is strongly associated with estrogen receptor-positive/progesterone receptor-negative tumors. Significant difference in estrogen receptor expression between high-grade and non-high-grade tumors with bone metastasis suggests that different panels of molecular markers should be used to predict bone metastasis in these 2 groups of tumors.
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PMID:Bone metastasis is strongly associated with estrogen receptor-positive/progesterone receptor-negative breast carcinomas. 1871 13

The most common forms of luminal breast cancer (BC) were compared with basal-like and Her2/neu3+ BC. Their primary classification was based on morphological diagnosis and the expression of estrogen receptor (ER), progesterone receptor (PR), and Her2/neu receptors. Monoclonal antibodies to actins and keratins were used for the study. Basal-like BC cells (ER/PR/Her2/ neu-) were regularly stained with antibodies to basal keratins 5/6 and 17, smooth muscle alpha-actin, and p63. Luminal keratin 8 staining was reduced. The solid regions had beta-actin staining with disappearance in the scirrhous component. beta-actin and basal keratins were also observed in metaplastic BC with ER/PR/Her2/neu3+. Immunomorphology using cytoskeletal markers along with the expression of steroid hormone and Her2/neu receptors may be used in the diagnosis of basal-like forms of BC.
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PMID:[Actins and keratins in the diagnosis of human basal-like breast cancer]. 2069 9

Breast cancer is currently the most common cancer in women worldwide. For this reason, new biomarkers for better predicting response to treatment are needed. CD40, described as expressed in haematological and epithelial tumors, is linked to apoptosis and offers promise as a new predictive/ prognostic marker. We evaluated CD40 expression in formalin-fixed, paraffin-embedded samples from 181 breast carcinomas using immunohistochemical staining with CD40 antibody. Samples were divided according to hormone (oestrogen receptor /ER/, progesterone receptor /PR/) and her-2/neu status into groups: 1.Luminal A (ER+PR+her-2/neu-), 2. Luminal B (ER+PR+her-2/neu+), 3.Triple-negative (ER-PR-her-2/neu-) and 4. Her-2/neu (ER-PR-her-2/neu+). The results of CD40 staining were correlated with clinicopathological data. CD40 was found to be expressed in membrane, cytoplasm and nucleus. Normal ducts expressed cytoplasmic CD40 in 30% of cases, in breast tumor ducts in 53% of cases. CD40 was evaluated as an independent marker and significant positive correlation was found with Bcl-2 (p =0.002), early stage (p =0.016) and preoperative chemotherapy (p =0.043). There was higher overall survival for patients with cytoplasmic CD40 expression (0.05). Differences in expression of cytoplasmic CD40 between groups with different hormonal and her-2/neu status were statistically highly significant (p=0.00003). In groups with different hormonal status, a positive statistical correlation was found for the luminal A group with relapse (p=0.024) and stage (p=0.006). No correlation was found with age, disease onset, family history of cancer/ breast cancer, patient history, hormonal replacement therapy, menopausal status at onset of disease, adjuvant chemotherapeutic treatment or disease free survival. Nuclear expression of CD40 was found to be unrelated to any clinicopathological data. However, there was higher ratio of positive cases in cancer cases (83%) than in normal tissue (30%). In conclusion, cytoplasmic expression of CD40 is related to factors connected to better prognosis and suggest that CD40 may have potential as a new prognostic factor in breast cancer.
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PMID:Analysis of CD40 expression in breast cancer and its relation to clinicopathological characteristics. 2139 34

We analyzed 75 cases of invasive ductal mammary carcinoma type NOS and focused on comparative investigation of hormonal receptors (estrogen receptor ER and progesterone receptor PR) and Her2/neu oncoprotein expression, according to which we ranked the cases in molecular classification subtypes, determining certain correlations between them and morphoclinical prognostic factors. 73.4% of cases were ER+ and 26.6% were ER-. PR was present in 62.6% of cases and absent in 37.4%. Phenotype ER+PR+ (58.6%) had the highest incidence, followed by ER-PR- (22.8%) and ER+PR- (14.6%). Phenotype ER-PR+ (4%) registered the lowest incidence. 14.8% of tumors were Her2/neu + score 3+, 4% had equivocal score 2+ and 81.3% were negative Her2/neu scored 0 and 1+. 9.5% of cases Her2/neu positive scored 3+ were ER+PR+ and 88.5% of cases Her2/neu negative scored 0-1 were ER+PR+. In terms of the correlation among the status of ER, PR and Her2/neu, we determined a molecular classification of the cases, obtaining the following incidences: luminal A 70% of cases, basal 14.7% of cases, luminal B 8.3%, the lowest incidence being registered at Her2, 7% of cases. Luminal A and basal subtypes were associated with patients aged over 50 years (82% for luminal A and 90% for basal), whereas luminal B and Her2 subtypes were registered mostly at patients aged under 60-year-old (83% for luminal B and 100% for Her2). Luminal A subtype was characterized by small tumors (92% of cases were T1-T2), well and moderately differentiated tumors (58% of cases were G1-G2). 83.3% of cases in luminal B subtype had tumors with dimensions ranked T2-T3, all cases being moderately and low differentiated. Her2 subtype had T2-T3 tumors in 60% of cases, which were G3 low differentiated in a percent of 80%. The basal subtype mostly had tumors larger than 5 cm (91% of cases were T2-T3), out of which only a case (9%) presented well-differentiated G1.
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PMID:Ductal invasive mammary carcinoma--clinicopathological prognostic factors related to immunohistochemical expression of hormonal receptors and Her2/neu oncoprotein. 2211 25

Molecular subtyping confirms that breast cancer comprises at least four genetically distinct entities based on the expression of specific genes including estrogen receptor (ER), progesterone receptor (PR), and HER2/neu receptor. The quantitative influence of subtype on ipsilateral locoregional recurrence (LRR) is unknown. The aim of this study was to systematically appraise the influence of breast cancer subtype on LRR following breast conserving therapy (BCT) and mastectomy. A comprehensive search for studies examining outcomes after BCT and/or mastectomy according to breast cancer subtype was performed using Medline and cross-referencing available data. Reviews of each study were conducted and data extracted to perform meta-analysis. Primary outcome was LRR related to breast cancer subtype. A total of 12,592 breast cancer patients who underwent either BCT (n = 7,174) or mastectomy (n = 5,418) were identified from 15 studies. Patients with luminal subtype tumors (ER/PR +ve) had a lower risk of LRR than both triple-negative (RR 0.38; 95% CI 0.23-0.61); and HER2/neu-overexpressing (RR 0.34; 95% CI 0.26-0.45) tumors following BCT. Luminal tumors were also less likely to develop LRR than HER2/neu-overexpressing (OR 0.69; 95% CI 0.54-0.89) or triple-negative tumors (OR 0.61; 95% CI 0.46-0.79) after mastectomy. HER2/neu-overexpressing tumors have increased risk of LRR compared to triple-negative tumors (RR 1.44; 95% CI 1.06-1.95) following BCT but there was no difference in LRR between HER2/neu-overexpressing and triple-negative tumors following mastectomy (RR 0.91; 95% CI 0.68-1.22). Luminal tumors exhibit the lowest rates of LRR. Patients with triple-negative and HER2/neu-overexpressing breast tumors are at increased risk of developing LRR following BCT or mastectomy. Breast cancer subtype should be taken into account when considering local control and identifies those at increased risk of LRR, who may benefit from more aggressive local treatment.
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PMID:Locoregional recurrence after breast cancer surgery: a systematic review by receptor phenotype. 2214 79

Breast cancer research and treatment by different subtypes is an inevitable trend. We investigated the clinicopathologic features and outcomes of different breast cancer subtypes in Southern China. A total of 5809 patients with invasive ductal carcinomas were identified. Immunohistochemical (IHC) markers for estrogen receptor (ER), progesterone receptor (PR), Her2/neu, and Ki-67 proliferation index were used to classify cases into five molecular subtypes. Clinicopathologic characteristics and survival rates were analyzed retrospectively. Of all patients, 31.1% were luminal A subtype, 30.4% luminal B (high Ki-67), 13.1% luminal B (Her2/neu+), 9.0% Her2/neu and 16.5% triple negative subtype. Luminal B (high Ki-67) presented primarily in premenopausal patients with the lowest average age (43.0 years). Her2/neu positive tumors were more closely associated with aggressive features including increased tumor size, positive lymph node status and lymphvascular invasion (LVI). Triple negative subtype was characterized by poorer histologic grade. Her2/neu positive cases had presented the worst 5-year disease-free survival (DFS) and overall survival (OS). Multivariate analyses of OS and DFS suggested that there were different negative prognostic factors for the five subtypes. The benefit of the cyclophosphamide, methotrexate, and 5-fluorouracil (5FU) (CMF) regimen was equal to that of anthracycline-based and Taxane-based regimens for patients with luminal A subtype and triple negative subtype, but inferior to anthracycline-based and Taxane-based regimens for those with two luminal B subtypes and Her2/neu subtype. The prognostic significance of traditional markers may differ among subtypes. This study revealed the distinct clinicopathologic characteristics, systemic therapy benefits, prognostic factors and survival rate among different breast cancer subtypes.
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PMID:Distribution, clinicopathologic features and survival of breast cancer subtypes in Southern China. 2262 27

Breast carcinoma may be classified into distinct molecular subtypes based on immunohistochemical markers for estrogen, progesterone and Her-2/neu receptors. The aim of the study was to identify the clinicopathological features of the molecular subtypes of breast carcinoma in our locality. A total of 274 surgically resected breast carcinomas were selected from the files of the Dr. KRZ referral pathology laboratory, Mansoura, Egypt, and the Pathology Department of Mansoura University. Molecular subtypes were classified into luminal A, luminal B, Her-2/neu-expressing and triple-negative. Clinicopathological and histological features of molecular subtypes were analyzed. Luminal A subtype was the most prevalent (41.2%), followed by triple-negative subtype (28.5%), then Her2-expressing subtype (19.4%) and luminal B subtype (13.9%). The commonest histological type was infiltrating duct carcinoma (83.2%), followed by infiltrating lobular carcinoma (9.1%) and medullary carcinoma (3.2%). The luminal A subtype was significantly correlated to low tumor grade, lower number of positive lymph nodes metastasis, absence of both necrosis and syncytial growth pattern. We concluded that the commonest molecular subtype of invasive breast carcinoma among Egyptian women is luminal subtype A, which displayed favorable features. Triple-negative subtype and medullary carcinomas are present in a ratio higher than in western countries.
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PMID:Molecular subtypes of breast carcinoma in Egyptian women: clinicopathological features. 2264 Oct 56

Breast cancer is the most commonly diagnosed cancer in women in United States. From data of American Cancer Society from 2007 reported total of 178,480 women diagnosed with breast cancer. The death rate from breast cancer has decreased in North America over time, but still accounts for second highest cancer death, following lung cancer. Breast cancer is staged based on tumor size, nodal involvement, and distant metastasis like any other solid tumors. However clinical staging is not the only important factor in management of breast cancer. Various molecular features divides breast cancer into many subgroups - that act differently, and respond differently from therapy. Thus the focus of breast cancer treatment has evolved focusing on specific targets. The most important biologic markers in subtyping of breast cancer so far are hormone receptor positivity and HER2/neu protein expression. Five molecular subtypes using intrinsic gene set include Basal mRNA, HER2 + mRNA, Luminal AmRNA, Luminal B mRNA, and Normal-like mRNA. In addition, better understanding of genetic target of breast cancer has given us arsenal of personalized, and more effective treatment approach.This review will focus on examples that highlight several mechanism of tumorigenesis, giving us not just understanding of gene pathways and the molecular biology, that could lead us to therapeutic target. Several important molecular targets have been investigated in preclinical and clinical trials, others are yet to be explored. We will also describe genetic mechanisms discovery related to overcoming resistance to current targeted therapies in breast cancer, including hormone receptor expression and HER 2- neu amplification. We will also review other exciting developments in understanding of breast cancer, the tumor microenvironment and cancer stem cells, and targeting agents in that area.
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PMID:Update on clinical trials: genetic targets in breast cancer. 2328 34

Literature shows that HER2/neu positive breast cancer cells are more sensitive to radiation-induced apoptosis by targeting the epidermal growth factor receptor family tyrosine kinase. We selected 466 patients with pT1-2 HER2/neu positive tumors who received adjuvant trastuzumab for primary invasive breast cancer. Patients were divided into three groups [Quadrantectomy followed by conventional radiotherapy vs Quadrantectomy followed by Intra-operative radiotherapy with electrons vs Mastectomy without radiotherapy]. After a median follow-up of 52 months, the 5-year cumulative incidence of locoregional recurrence (LRR) was 1.9%, 11.5% and 5.0% respectively (p < 0.01). At the multivariate analysis, extensive perivascular invasion, Luminal B HER2/Progesterone Receptor (PgR) negative status and Quadrantectomy followed by Intra-operative radiotherapy with electrons have significantly increased the risk of LRR. Our results suggest that HER2/neu positive breast cancer might have better outcomes when treated simultaneously with external radiotherapy and trastuzumab. Moreover, we underline the importance of PgR and further new stratification of risk among luminal subtypes.
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PMID:Locoregional recurrence in patients with HER2 positive breast cancer. 2364 29


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