Significance of epidermal growth factor receptor expression in breast cancer

Colorectal cancer is one of the most common cancers worldwide. The anticancer effect of Wolfberry (Lycium barbarum) polysaccharide (LBP) on colon cancer cells is largely unknown. To investigate the growth effect of LBP on human colon cancer cell and its possible mechanisms, human colon cancer SW480 and Caco-2 cells were treated with 100–1,000 mg/l LBP for 1–8 days. Cell growth was measured by MTT assay and crystal violet assay. Distribution of the cell cycle was analyzed by flow cytometry. Western blotting was used to indicate changes in the level of cyclins and cyclin-dependent kinases (CDKs). LBP treatment inhibited both colon cancer cell lines in a dose-dependent manner. At concentrations from 400 to 1,000 mg/l, LBP significantly inhibited the growth of SW480 cells (400 mg/l, P < 0.01; 800 and 1,000 mg/l, P < 0.001); while at concentrations from 200 to 1,000 mg/l, LBP significantly inhibited the growth of Caco-2 cells (200 mg/l, P < 0.05; 400–1,000 mg/l, P < 0.001). Crystal violet assay showed that LBP had a long-term anti-proliferative effect. More importantly, cells were arrested at the G0/G1 phase. The changes in cell-cycle-associated protein, cyclins, and CDKs were consistent with the changes in cell-cycle distribution. This is one of the first studies to focus on LBP-induced interruption of the cell cycle in human colon carcinoma cells. The results suggest that LBP is a candidate anticancer agent.     

Significance of epidermal growth factor receptor expression in breast cancer

Recent interest of many investigators is focused on epidermal growth factor receptor (EGFR) family, because of their potential role in the pathogenesis and progression of breast cancer. Paraffin tumor sections were collected retrospectively from 181 breast cancer patients diagnosed between 2002 and 2003. Immunohistochemical staining with ErbB-1, ErbB-2, ErbB-3, and ErbB-4 monoclonal antibodies was performed. The ErbB expression was correlated with the other clinicopathological variables. Overexpression of ErbB-1, ErbB-2, ErbB-3, and ErbB-4 was observed in 20.6, 18.2, 14.3, and 5.7% cases, respectively. Overexpression of ErbB-1 and ErbB-2 was associated with poor prognostic features and decreased 5-year disease-free survival. The patients with co-overexpression of ErbB-1 and ErbB-2 had a shorter DFS, although this difference was not statistically significant. ErbB-1 overexpression may indicate a subset of patients with a poor disease prognosis. Assays for ErbB-1 and ErbB-2 may be more useful than a single assay in predicting prognosis of a breast cancer patient.     

Immunohistochemical expression of epidermal growth factor receptor in breast cancer

Background  

Molecular-targeting drugs able to treat breast cancer expressing epidermal growth factor receptor (EGFR) would be clinically valuable. The aim of the current study was to determine the further significance of immunohistochemical expression of EGFR in breast cancer.     

Significance of epidermal growth factor receptor expression in breast cancer

Recent interest of many investigators is focused on epidermal growth factor receptor (EGFR) family, because of their potential role in the pathogenesis and progression of breast cancer. Paraffin tumor sections were collected retrospectively from 181 breast cancer patients diagnosed between 2002 and 2003. Immunohistochemical staining with ErbB-1, ErbB-2, ErbB-3, and ErbB-4 monoclonal antibodies was performed. The ErbB expression was correlated with the other clinicopathological variables. Overexpression of ErbB-1, ErbB-2, ErbB-3, and ErbB-4 was observed in 20.6, 18.2, 14.3, and 5.7% cases, respectively. Overexpression of ErbB-1 and ErbB-2 was associated with poor prognostic features and decreased 5-year disease-free survival. The patients with co-overexpression of ErbB-1 and ErbB-2 had a shorter DFS, although this difference was not statistically significant. ErbB-1 overexpression may indicate a subset of patients with a poor disease prognosis. Assays for ErbB-1 and ErbB-2 may be more useful than a single assay in predicting prognosis of a breast cancer patient.

     

Serum epidermal growth factor receptor and HER2 expression in primary and metastatic breast cancer patients

Background  

Breast tissue expression of the ERBB proto-oncogene family has been extensively studied. It was recently shown that expression of epidermal growth factor receptor (EGFR; c-erbB-1) and epidermal growth factor receptor (HER)2 (c-erbB-2) can be detected in the serum of breast cancer patients. The clinical relevance of this has not been fully established.     

Role of epidermal growth factor receptor in breast cancer

Decades of research in molecular oncology have brought about promising new therapies which are designed to target specific molecules which promote tumor growth and survival. The epidermal growth factor receptor (EGFR) is one of the first identified important targets of these novel antitumor agents. Approximately half of cases of triple-negative breast cancer (TNBC) and inflammatory breast cancer (IBC) overexpress EGFR. Thus, EGFR inhibitors for treatment of breast cancer have been evaluated in several studies. However, results so far have been disappointing. One of the reasons for these unexpected results is the lack of biomarkers for predicting which patients are most likely to respond to EGFR inhibitors. Recent studies have shown that EGFR and its downstream pathway regulate epithelial-mesenchymal transition, migration, and tumor invasion and that high EGFR expression is an independent predictor of poor prognosis in IBC. Further, recent studies have shown that targeting EGFR enhances the chemosensitivity of TNBC cells by rewiring apoptotic signaling networks in TNBC. These studies indicate that EGFR-targeted therapy might have a promising role in TNBC and IBC. Further studies of the role of EGFR in TNBC and IBC are needed to better understand the best way to use EGFR-targeted therapy??e.g., as a chemosensitizer or to prevent metastases??to treat these aggressive diseases.     

Involvement of epidermal growth factor receptor overexpression in the promotion of breast cancer brain metastasis

BACKGROUND:

Brain‐metastatic breast cancer (BMBC) is increasing and poses a severe clinical problem because of the lack of effective treatments and because the underlying molecular mechanisms are largely unknown. Recent work has demonstrated that deregulation of epidermal growth factor receptor (EGFR) may correlate with BMBC progression. However, the exact contribution that EGFR makes to BMBC remains unclear.

METHODS:

The role of EGFR in BMBC was explored by serial analyses in a brain‐trophic clone of human MDA‐MB‐231 breast carcinoma cells (231‐BR cells). EGFR expression was inhibited by stable short‐hairpin RNA transfection or by the kinase inhibitor erlotinib, and it was activated by heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF). Cell growth and invasion activities also were analyzed in vitro and in vivo.

RESULTS:

EGFR inhibition or activation strongly affected 231‐BR cell migration/invasion activities as assessed by an adhesion assay, a wound‐healing assay, a Boyden chamber invasion assay, and cytoskeleton staining. Also, EGFR inhibition significantly decreased brain metastases of 231‐BR cells in vivo. Surprisingly, changes to EGFR expression affected cell proliferation activities less significantly as determined by a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, an anchorage‐independent growth assay, and cell cycle analysis. Immunoblot analysis suggested that EGFR drives cells' invasiveness capability mainly through phosphoinositide 3‐kinase/protein kinase B and phospholipase C γ downstream pathways. In addition, EGFR was involved less in proliferation because of the insensitivity of the downstream mitogen‐activated protein kinase pathway.

CONCLUSIONS:

The current results indicated that EGFR plays more important roles in cell migration and invasion to the brain than in cell proliferation progression on 231‐BR cells, providing new evidence of the potential value of EGFR inhibition in treating BMBC. Cancer 2012. © 2012 American Cancer Society.     

受体O型蛋白酪氨酸磷酸酶与表皮生长因子受体2在乳腺癌中表达的相关性

目的:分析受体0型蛋白酪氨酸磷酸酶(PTPRO)与表皮生长因子受体2(HER2)在乳腺癌中的表达及其临床意义.方法:采用免疫组织化学EnVision法检测50例原发乳腺癌组织中PTPRO与HER2的表达状态并结合临床病理资料进行统计分析.结果:乳腺癌组织中PTPRO阳性表达率40.0％(20/50),PTPRO表达缺失同淋巴结转移和孕激素受体表达相关(P ＜0.05);HER2阳性表达率68％ (34/50),同肿瘤大小、淋巴结转移和孕激素受体表达相关(P＜0.05).PTPRO与HER2表达呈负相关(P =0.026).结论:PTPRO与HER2表达同乳腺癌临床病理特征密切相关,联合检测二者具有潜在的临床诊断意义.     

Expression of epidermal growth factor receptor in urinary bladder cancer metastases

Bladder cancers frequently exhibit an increased number of epidermal growth factor receptors (EGFR) in comparison to normal urothelium. The EGFR could potentially be a target for toxic conjugates. The aim of our study was to compare the expression of EGFR in metastases with concurrent or primary tumour in the urinary bladder using immunohistochemical techniques and a monoclonal antibody. Tumour material from 20 patients was investigated. The majority (13/20) of the metastases were homogeneously stained and showed a moderate to strong membranous staining for EGFR. The expression of EGFR in primary bladder tumours and metastases was similar. There was no indication that tumour tissue exposed to chemotherapy or radiation had a decreased number of EGFR. Targeting of the EGFR thus seems potentially applicable to metastatic disease. Int. J. Cancer 76:189–193, 1998.© 1998 Wiley-Liss, Inc.     

A meta-analysis of oestrogen receptor,progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases

BackgroundThe discordance in oestrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) status between primary and recurrent breast cancer is being intensively investigated and a large amount of data have been produced. However, results from different studies are heterogeneous and often conflicting. To highlight this issue, a meta-analysis of published data was performed.MethodsA literature search was performed using Medline, and all the studies published from 1983 to 2011 comparing changes in ER, PgR and/or HER2 status in patients with matched breast primary and recurrent tumours were included. We used random-effects models to estimate pooled discordance proportions.ResultsWe selected 48 articles, mostly reporting retrospective studies. Thirty-three, 24 and 31 articles were focused on ER, PgR and HER2 changes, respectively. A total of 4200, 2739 and 2987 tumours were evaluated for ER, PgR and HER2 discordance, respectively. The heterogeneity between study-specific discordance proportions was high for ER (I² = 91%, p < 0.0001), PgR (I² = 79%, p < 0.0001) and HER2 (I² = 77%, p < 0.0001). Pooled discordance proportions were 20% (95% confidence interval (CI): 16–35%) for ER, 33% (95% CI: 29–38%) for PgR and 8% (95% CI: 6–10%) for HER2. Pooled proportions of tumours shifting from positive to negative and from negative to positive were 24% and 14% for ER (p = 0.0183), respectively. The same figures were 46% and 15% for PgR (p < 0.0001), and 13% and 5% for HER2 (p = 0.0004).ConclusionOur findings strengthen the concept that changes in receptor expression may occur during the natural history of breast cancer, suggesting clinical implications and a possible impact on treatment choice.     

Relationship of epidermal growth factor receptor expression to ErbB-2 signaling activity and prognosis in breast cancer patients.

PURPOSE: To examine the relationship of epidermal growth factor receptor (EGFR) expression to ErbB-2 signaling activity in breast cancer and the impact that this interaction has on the prognosis of patients with early-stage breast cancer. PATIENTS AND METHODS: Paraffin tumor sections were collected retrospectively from 807 breast cancer patients diagnosed between 1976 and 1983. Immunohistochemical assays for ErbB-2, phosphorylated (activated) ErbB-2, and EGFR were performed, and the results were correlated with clinicopathologic variables and outcome. RESULTS: EGFR expression was detectable in 15% of 807 invasive breast cancers, including 35% of the 306 ErbB-2-positive patients. Conversely, the majority (87%) of EGFR-positive tumors co-overexpressed ErbB-2. Ninety-seven percent of tumors with phosphorylated ErbB-2 co-overexpressed EGFR. Patients whose cancers demonstrated ErbB-2 phosphorylation or co-overexpression of ErbB-2 and EGFR had the shortest survival. In contrast, patients whose tumors were negative for all three markers and those tumors that expressed only EGFR or only nonphosphorylated ErbB-2 had a relatively favorable outcome. CONCLUSION: These data provide the first clinical evidence that EGFR expression is linked to activation of ErbB-2 in human breast cancers. We have further shown that the adverse prognostic value of ErbB-2 overexpression is observed only when ErbB-2 is in the phosphorylated (activated) state or coexpressed with EGFR. These data suggest that ligand-dependent mechanisms of ErbB-2 activation are important in human breast cancer. These results also suggest that agents targeting EGFR may be useful in the treatment of tumors with activated ErbB-2.     

Ribociclib for the treatment of hormone receptor-positive,human epidermal growth factor receptor 2-negative advanced breast cancer

Introduction: The emergence of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors marked a significant advancement in the treatment of advanced breast cancer. Ribociclib is an orally bioavailable, highly selective inhibitor of CDK4/6. In combination with various endocrine therapies, ribociclib has demonstrated clinical activity as a first-line therapy for patients with HR+, HER2? advanced breast cancer, without compromising the favorable toxicity profile associated with endocrine therapy. Thus, ribociclib is now considered a new standard of care for HR+, HER2? advanced breast cancer.

Areas covered: This review provides a concise overview of the preclinical and clinical development of ribociclib, including evidence of its clinical activity and safety profile when combined with endocrine therapy in HR+, HER2? advanced breast cancer.

Expert commentary: CDK4/6 inhibition represents a promising treatment option for patients with HR+ metastatic breast cancer. Ribociclib significantly improved progression-free survival in patients receiving first-line endocrine therapy for HR+, HER2? advanced breast cancer. Planned and ongoing trials investigating ribociclib in combination with other endocrine therapies and in various clinical settings will help to determine the optimal treatment sequence for different patient populations.     

激素受体阳性人表皮生长因子受体2阳性乳腺癌分子分型与异质性的研究进展

激素受体阳性人表皮生长因子受体2阳性（HR + HER2 +）乳腺癌是一类具有高度异质性的疾病,约占乳腺癌10%。各亚型的分子生物学特征、药物治疗疗效及预后有显著差异。文章将以异质性为切入点,对HR + HER2 +乳腺癌的分子生物学特征、诊疗现状及单细胞水平研究进展进行综述。 ...     

Obesity increases the incidence of distant metastases in oestrogen receptor-negative human epidermal growth factor receptor 2-positive breast cancer patients

BackgroundObesity is a major negative determinant of breast cancer outcome. However, there are contrasting data on the differential impact of obesity on specific breast cancer subtypes. In particular, very little is known on human epidermal growth factor receptor 2-positive (HER2+) tumours.Patients and methodsWe assessed the prognostic role of increased body mass index (BMI) on a consecutive series of non-metastatic HER2+ patients treated at our institution before the introduction of adjuvant Trastuzumab. We separately analysed oestrogen receptor-positive (ER+) and -negative (ER?) HER2+ cases.ResultsIn ER?/HER2+ tumours we observed a significantly worse overall survival (Hazard ratio (HR) 1.79, p-value 0.041) and cumulative incidence of distant metastases (HR 2.03, p-value 0.019) in obese (BMI > 30) versus normal/underweight (BMI < 25) patients. Local relapses appeared to be non-significantly reduced in obese patients, masking the overall effect on disease-free survival. Outcome in ER+ tumours, instead, was not significantly different between BMI groups.ConclusionsObesity significantly correlates with worse overall survival and cumulative incidence of distant metastases in ER?/HER2 positive breast cancer. Differences in the biology of breast tumours may determine individual susceptibility to obesity. The biology of the underlying tumour should be taken into account in the design of dietary intervention trials in breast cancer.     

Prognostic value of p53 expression in hormone receptor-positive and human epidermal growth factor receptor 2-negative breast cancer patients receiving neoadjuvant chemotherapy

Breast Cancer Research and Treatment - The aim of this study was to determine whether the outcome to neoadjuvant chemotherapy (NAC) can be predicted by analyzing p53 expression in hormone receptor...     

人表皮生长因子受体-2及雌激素受体与乳腺癌的关系

乳腺癌与人表皮生长因子受体-2及雌激素受体关系密切,这两种受体也是乳腺癌的分类标准和治疗靶点。在大多数乳腺癌患者中,人表皮生长因子受体-2信号途径和雌激素受体信号途径参与了细胞的增生存活过程。而且在乳腺癌病例中,人表皮生长因子受体-2和雌激素受体呈现出一定程度的负相关。这说明这两种受体活化后有一些联系。本文简要综述了人表皮生长因子受体-2和雌激素受体的联系以及这种联系在乳腺癌治疗中的意义。