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.

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.

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.

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

Neoadjuvant Trastuzumab Induces Apoptosis in Primary Breast Cancers

2005 ◽  
Vol 23 (11) ◽  
pp. 2460-2468 ◽  
Author(s):  
Syed K. Mohsin ◽  
Heidi L. Weiss ◽  
M. Carolina Gutierrez ◽  
Gary C. Chamness ◽  
Rachel Schiff ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cellular Response ◽  
Single Agent ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Her 2 ◽  
Epidermal Growth

Purpose Greater understanding of the cellular response in trastuzumab-treated patients will provide insight into the clinical management of patients. Patients and Methods We performed a neoadjuvant trial in 35 patients with locally advanced HER-2/neu overexpressing breast cancers who received weekly trastuzumab given as a single agent for the first 3 weeks, followed by a combination of trastuzumab and docetaxel for 12 weeks before surgery. Sequential core biopsies were taken at baseline and within weeks 1 and 3 after the first dose of trastuzumab. Clinical response to trastuzumab was assessed by tumor measurements on day 22 before chemotherapy. Core biopsies were assessed by immunohistochemistry for cell cycle and proliferation (Ki67, p27, phosphorylated [p] -MAPK), apoptosis and survival (apoptotic index, p-Akt), epidermal growth factor receptor, and total and p-HER-2. Results There was early tumor regression with a median decrease of −20.0% (range. 0% to 60.4%) after only 3 weeks of trastuzumab, and eight patients (23%) had a partial response. Consistent with the clinical regressions, apoptosis was significantly induced (median increase from 3.5% to 4.7%; P = .006) within week 1, a 35% increase above baseline. No significant change in epidermal growth factor receptor score was observed in week 1, without changes in total or p-HER-2 expression. Tumors with high baseline Ki67 were less likely to respond (P = .02). Conclusion In primary breast cancers, trastuzumab substantially induces apoptosis, providing a molecular explanation for both its therapeutic efficacy and its successful combination with cytotoxic chemotherapy.

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

scholarly journals Human epidermal growth factor receptor 2/neu and the clinico-pathological profile in breast cancer: an observational study at a tertiary care hospital in Central India

2021 ◽  
Vol 8 (12) ◽  
pp. 3649
Author(s):  
Shikha Shukla ◽  
Fahad Ansari
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Breast Carcinoma ◽  
Epidermal Growth Factor ◽  
Cancer Patients ◽  
Growth Factor Receptor ◽  
Breast Cancer Patients ◽  
Her 2 ◽  
Epidermal Growth

Background: Breast cancer is the most commonly occurring cancer in women and the second most common cancer overall. Owing to a unique pattern of presentation in terms of clinical and biological features, finding their mutual association may be important and may help predict prognosis. HER2 (human epidermal growth factor receptor 2)/neu is one such important immunohistochemical factor that is considered to be more prevalent amongst Indians and therefore makes up for an emerging area for studies. The study aimed to assess the patients of breast carcinoma in terms of their HER2/neu statuses and find out their association with clinical parameters.Methods: This was a prospective comparative study conducted in department of surgery, Hamidia hospital, Bhopal, India, with a total duration of 1 year between November 2018 to September 2019 including a total of 98 consecutive in house breast carcinoma patients.Results: A total of 98 breast cancer patients were tested for HER-2/neu gene presence. Of these 25 (25.5%) samples tested positive and 73 (7.48%) tested negative. A comparison of the two groups revealed that none of the clinic-pathological factors tested were found to have a statistically significant association with the HER2/neu status.Conclusions: It appeared that there is no defining factor in terms of clinic-pathological presentation that helps to separate significantly HER-2/neu positive with HER-2/neu negative cases with breast cancer. Still, immune-histochemical marker analysis should be an integral part of the overall work up of the breast cancer patients because of its both prognostic and therapeutic application and significance.

Triple Negative Breast Cancer: A Brief Review of its Characteristics and Treatment Options

2012 ◽  
Vol 25 (3) ◽  
pp. 319-323 ◽  
Author(s):  
Carrie L. Griffiths ◽  
Jacqueline L. Olin
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Her 2 ◽  
Epidermal Growth

Triple negative breast cancer (TNBC), an aggressive variant of breast cancer, is characterized by lack of expression of the estrogen (ER) and progesterone receptors (PRs) and the human epidermal growth factor receptor (HER-2) that are commonly observed in other breast cancer subtypes. The TNBC subtype primarily occurs in younger women of African American or Hispanic descent and tumors tend to be high grade and initially responsive to chemotherapy. However, TNBC is characteristically aggressive with high recurrence, metastatic, and mortality rates. Treatment options are limited since the hormonal receptor and HER-2 antagonists typically used for other breast cancers are ineffective. As such, the mainstay of treatment of TNBC is traditional systemic cytotoxic chemotherapy. Potential future therapies for TNBC include targeted molecular strategies including poly (adenosine diphosphate ribose) polymerase (PARP) and epidermal growth factor receptor (EGFR) inhibitors and antiangiogenic agents. Further research aimed at identifying unique genetic characteristics of TNBC may allow development of other targeted molecular chemotherapy treatment options.

Radioimmunohistochemistry of Epidermal Growth Factor Receptor in Breast Cancer

2002 ◽  
Vol 126 (2) ◽  
pp. 177-181
Author(s):  
Kevin W. Robertson ◽  
Jonathon R. Reeves ◽  
Alison K. Lannigan ◽  
James J. Going ◽  
Timothy G. Cooke ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Lines ◽  
Dynamic Range ◽  
Growth Factor Receptor ◽  
Prognostic Indicators ◽  
Egfr Expression ◽  
Epidermal Growth

Abstract Context.—Conflicting reports of epidermal growth factor receptor (EGFR) expression in breast cancer and inconstant relationships with established prognostic indicators and outcomes suggest difficulties with EGFR measurement. Objective.—To compare EGFR measurement in a panel of cell lines and in breast carcinomas by radioimmunohistochemistry (R-IHC), conventional immunohistochemistry (IHC), and a ligand binding (LB) assay. Design.—Eight EGFR-expressing cell lines and 50 primary breast carcinoma specimens were analyzed for EGFR by IHC, R-IHC, and LB assays. A further 153 primary breast cancer specimens were analyzed by R-IHC alone. Results.—All 3 assays were in good agreement for the cell lines. In the subset of the 50 carcinoma specimens, EGFR was detected by LB assays in 19 (38%) and by IHC in 24 (48%). However, R-IHC detected EGFR in 46 (92%) of 50 and in 186 (92%) of all 203 carcinoma specimens. The LB assay agreed poorly with R-IHC of carcinomas, possibly because the LB assay is sensitive to EGFR-expressing nontumor breast parenchyma in the tissue analyzed. Both IHC and R-IHC on carcinoma specimens agreed better, but 26 carcinoma specimens (52%) in which EGFR was not detectable by IHC had a 10-fold range in receptor level detectable by R-IHC. Conclusion.—To elucidate the role of EGFR or other growth factor receptors in breast cancer requires accurate, sensitive receptor assays. With its dynamic range, R-IHC returned meaningful results over the entire range of expression actually present in breast cancer, which LB assays and IHC failed to do.

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