Prognostic Significance of Overexpression and Phosphorylation of Epidermal Growth Factor Receptor (EGFR) and the Presence of Truncated EGFRvIII in Locoregionally Advanced Breast Cancer

2007 ◽  
Vol 25 (28) ◽  
pp. 4405-4413 ◽  
Author(s):  
Yago Nieto ◽  
Fatima Nawaz ◽  
Roy B. Jones ◽  
Elizabeth J. Shpall ◽  
Samia Nawaz
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Prognostic Value ◽  
Growth Factor Receptor ◽  
High Dose ◽  
Egfr Expression ◽  
Her 2 ◽  
Epidermal Growth

Purpose The prognostic value of the epidermal growth factor receptor (EGFR) in breast cancer and more specifically, in patients with locoregionally advanced disease, is still undefined. We hypothesized that EGFR status plays a major prognostic role in this setting, through expression, activation, or the presence of its mutated variant EGFRvIII. Patients and Methods We reviewed tumor samples of 225 patients treated uniformly in prospective trials of high-dose chemotherapy for four to nine positive axillary nodes, ≥ 10 positive nodes, or inflammatory carcinoma, and observed for a median of 9 years (range, 3 to 13 years). We analyzed the effect on outcome of expression of EGFR, phosphorylated EGFR (phospho-EGFR), and EGFRvIII, as studied by immunohistochemistry. Results EGFR expression, phospho-EGFR, and mutated EGFRvIII were detected in 43%, 54%, and 4% of the patients, respectively. EGFR expression correlated with negative hormone receptor status, and was associated with significantly worse relapse-free survival (59% v 79%; P < .001) and overall survival (61% v 81%; P = .001) than no expression. There was no association of phospho-EGFR or EGFRvIII with outcome. Multivariate models confirmed the prognostic effect of EGFR independent of other known prognostic variables in this population. The prognostic value of EGFR was most prominent in the human epidermal growth factor receptor 2 (HER-2) –positive and the estrogen receptor/progesterone receptor–negative subgroups. Conclusion EGFR expression, but not phospho-EGFR or EGFRvIII expression, is an independent adverse prognostic factor in patients with high-risk primary breast cancer, particularly when it is coexpressed with HER-2. Our results suggest the potential benefit of dual EGFR/HER-2 receptor targeting in this setting.

Young Age at Diagnosis Correlates With Worse Prognosis and Defines a Subset of Breast Cancers With Shared Patterns of Gene Expression

2008 ◽  
Vol 26 (20) ◽  
pp. 3324-3330 ◽  
Author(s):  
Carey K. Anders ◽  
David S. Hsu ◽  
Gloria Broadwater ◽  
Chaitanya R. Acharya ◽  
John A. Foekens ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Young Women ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Egfr Expression ◽  
Her 2 ◽  
Epidermal Growth

Purpose Breast cancer arising in young women is correlated with inferior survival and higher incidence of negative clinicopathologic features. The biology driving this aggressive disease has yet to be defined. Patients and Methods Clinically annotated, microarray data from 784 early-stage breast cancers were identified, and prospectively defined, age-specific cohorts (young: ≤ 45 years, n = 200; older: ≥ 65 years, n = 211) were compared by prognosis, clinicopathologic variables, mRNA expression values, single-gene analysis, and gene set enrichment analysis (GSEA). Univariate and multivariate analyses were performed. Results Using clinicopathologic variables, young women illustrated lower estrogen receptor (ER) positivity (immunohistochemistry [IHC], P = .027), larger tumors (P = .012), higher human epidermal growth factor receptor 2 (HER-2) overexpression (IHC, P = .075), lymph node positivity (P = .008), higher grade tumors (P < .0001), and trends toward inferior disease-free survival (DFS; hazard ratio = 1.32; P = .094). Using genomic expression analysis, tumors arising in young women had significantly lower ERα mRNA (P < .0001), ERβ (P = .02), and progesterone receptor (PR) expression (P < .0001), but higher HER-2 (P < .0001) and epidermal growth factor receptor (EGFR) expression (P < .0001). Exploratory analysis (GSEA) revealed 367 biologically relevant gene sets significantly distinguishing breast tumors arising in young women. Combining clinicopathologic and genomic variables among tumors arising in young women demonstrated that younger age and lower ERβ and higher EGFR mRNA expression were significant predictors of inferior DFS. Conclusion This large-scale genomic analysis illustrates that breast cancer arising in young women is a unique biologic entity driven by unifying oncogenic signaling pathways, is characterized by less hormone sensitivity and higher HER-2/EGFR expression, and warrants further study to offer this poor-prognosis group of women better preventative and therapeutic options.

scholarly journals Modulation of EGFR Gene Transcription by a Polymorphic Repetitive Sequence – a Link between Genetics and Epigenetics

2000 ◽  
Vol 15 (1) ◽  
pp. 105-110 ◽  
Author(s):  
F. Gebhardt ◽  
H. BÜrger ◽  
B. Brandt
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Model Calculations ◽  
Ca Repeat ◽  
Egfr Gene ◽  
Egfr Expression ◽  
Epidermal Growth

The epidermal growth factor receptor (EGFR) plays a crucial role in growth, differentiation and motility of normal as well as tumor cells. The transduction of extracellular signals to the cytoplasm via the receptor not only depends on ligand binding, but is also determined by the receptor density on the cell surface. Therefore, with regard to cancer diagnosis and therapeutic approaches targeting EGFR it is important to know how the expression level of EGFR is controlled. We found that transcription activity declines with increasing numbers of CA dinucleotides of a highly polymorphic CA repeat in the first intron of the epidermal growth factor receptor gene. In vivo data from cultured cell lines support these findings, although other regulation mechanisms can compensate this effect. In addition, we showed that RNA elongation terminates at a site closely downstream of the simple sequence repeat (SSR) and that there are two separate major transcription start sites. Model calculations for the helical DNA conformation revealed a high bendability in the EGFR polymorphic region, especially if the CA stretch is extended. These data suggest that the CA-SSR can act like a joint, bringing the promoter in proximity to a putative repressor protein bound downstream of the CA-SSR. The data indicate that this polymorphism may be a marker for cancer, linking genetic and epigenetic risk factors. Furthermore, in breast cancer, heterozygous tumors with short CA-SSR showed an elevated EGFR-expression in contrast to tumours with longer CA-SSR. Tumours with loss of heterozygosity in intron 1 of egfr revealed an increased EGFR expression if the longer allele was lost. Moreover, decreased EGFR gene levels were significantly correlated with poor prognosis in breast cancer.

Prognostic value of epidermal growth factor receptor (EGFR) family members in breast cancer.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. e21079-e21079
Author(s):  
T. Badovinac Crnjevic ◽  
J. Jakic-Razumovic ◽  
D. Vrbanec ◽  
A. Juretic ◽  
S. Plestina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Prognostic Value ◽  
Family Members ◽  
Growth Factor Receptor ◽  
Epidermal Growth ◽  
Egfr Family

scholarly journals Phase II Trial of Lapatinib for Brain Metastases in Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

2008 ◽  
Vol 26 (12) ◽  
pp. 1993-1999 ◽  
Author(s):  
Nancy U. Lin ◽  
Lisa A. Carey ◽  
Minetta C. Liu ◽  
Jerry Younger ◽  
Steven E. Come ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Brain Metastases ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Her 2 ◽  
Epidermal Growth ◽  
Positive Breast Cancer

PurposeOne third of women with advanced human epidermal growth factor receptor 2 (HER-2)–positive breast cancer develop brain metastases; a subset progress in the CNS despite standard approaches. Medical therapies for refractory brain metastases are neither well-studied nor established. We evaluated the safety and efficacy of lapatinib, an oral inhibitor of epidermal growth factor receptor (EGFR) and HER-2, in patients with HER-2–positive brain metastases.Patients and MethodsPatients had HER-2–positive breast cancer, progressive brain metastases, prior trastuzumab treatment, and at least one measurable metastatic brain lesion. Patients received lapatinib 750 mg orally twice a day. Tumor response was assessed by magnetic resonance imaging every 8 weeks. The primary end point was objective response (complete response [CR] plus partial response [PR]) in the CNS by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points included objective response in non-CNS sites, time to progression, overall survival, and toxicity.ResultsThirty-nine patients were enrolled. All patients had developed brain metastases while receiving trastuzumab; 37 had progressed after prior radiation. One patient achieved a PR in the brain by RECIST (objective response rate 2.6%, 95% conditional CI, 0.21% to 26%). Seven patients (18%) were progression free in both CNS and non-CNS sites at 16 weeks. Exploratory analyses identified additional patients with some degree of volumetric reduction in brain tumor burden. The most common adverse events (AEs) were diarrhea (grade 3, 21%) and fatigue (grade 3, 15%).ConclusionThe study did not meet the predefined criteria for antitumor activity in highly refractory patients with HER-2–positive brain metastases. Because of the volumetric changes observed in our exploratory analysis, further studies are underway utilizing volumetric changes as a primary end point.

Expression Analyses of Epidermal Growth Factor Receptor and HER-2/neu: No Advantage of Prediction of Recurrence or Survival in Breast Cancer Patients

Oncology ◽  
1996 ◽  
Vol 53 (6) ◽  
pp. 441-447 ◽  
Author(s):  
Matthias W. Beckmann ◽  
Dieter Niederacher ◽  
Gero Massenkeil ◽  
Boris Tutschek ◽  
Andreas Beckmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cancer Patients ◽  
Growth Factor Receptor ◽  
Breast Cancer Patients ◽  
Her 2 ◽  
Epidermal Growth

Prognostic value of the combination of epidermal growth factor receptor and c-erbB-2 in breast cancer

Surgery ◽  
2003 ◽  
Vol 133 (2) ◽  
pp. 219-221 ◽  
Author(s):  
Shinichi Tsutsui ◽  
Shinji Ohno ◽  
Shigeru Murakami ◽  
Akemi Kataoka ◽  
Junko Kinoshita ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Prognostic Value ◽  
Growth Factor Receptor ◽  
Epidermal Growth

scholarly journals Serum epidermal growth factor receptor/HER-2 predicts poor survival in patients with metastatic breast cancer

Cancer ◽  
2006 ◽  
Vol 107 (10) ◽  
pp. 2337-2345 ◽  
Author(s):  
Christopher Souder ◽  
Kim Leitzel ◽  
Suhail M. Ali ◽  
Laurence Demers ◽  
Dean B. Evans ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Metastatic Breast Cancer ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Poor Survival ◽  
Her 2 ◽  
Epidermal Growth
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