EGFR expression and gene copy number in triple-negative breast carcinoma

Gumuskaya, Berrak; Alper, Murat; Hücümenoğlu, Sema; Altundağ, Kadri̇; Üner, Ayşegül; Güler, Gülnur

doi:10.1016/j.cancergencyto.2010.07.118

Cited by 63 publications

(57 citation statements)

References 27 publications

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“…30,31 We also assessed EGFR amplification by the University of Colorado Cancer Center criteria and found that EGFR amplification was quite rare, being present in only 2% of cases, which is consistent with some previous studies. 10,19,25 However, EGFR high polysomy was found in 31% of cases, which is relatively higher than in previous studies. This result may be related to the heterogeneity of high polysomy in some cases, which will be discussed later.…”

Section: Discussioncontrasting

confidence: 72%

“…Several groups that used in situ hybridization technique reported significant correlations between EGFR protein overexpression and high gene copy in triple-negative breast cancer. 10,13,14,19 However, Martin et al 11 and Toyama et al 17 showed no correlation between EGFR immunoexpression and increased EGFR gene copy number. In this study, EGFR overexpression was generally correlated with high EGFR copy number.…”

Section: Discussionmentioning

confidence: 98%

“…EGFR gene amplification and high polysomy were reported in up to 24% and 27% of triple-negative breast cancer, respectively (Table 8). 10,11,13,14,19,25 However, the frequency of EGFR gene amplification is quite variable, even though most studies used the same, University of Colorado Cancer Center criteria. 30,31 We also assessed EGFR amplification by the University of Colorado Cancer Center criteria and found that EGFR amplification was quite rare, being present in only 2% of cases, which is consistent with some previous studies.…”

Section: Discussionmentioning

confidence: 99%

“…8 EGFR is a well-established treatment target for colorectal cancer, non-small cell lung cancer, and squamous cell carcinoma of the head and neck. In breast cancer, EGFR overexpression has been reported in up to 78% of triple-negative breast cancers, [9][10][11][12][13][14][15][16][17][18][19][20] more than in non-triple-negative breast cancers, 12,15 suggesting that EGFR is a potential therapeutic target for triple-negative breast cancer. EGFR tyrosine kinase inhibitors have yielded insignificant response rates in breast cancer, [21][22][23] possibly due to the lack of patient selection in these studies; they were not restricted to breast cancers with EGFR overexpression or triple-negative breast cancers.…”

Section: Introductionmentioning

confidence: 99%

“…24 EGFR gene amplification, one of the mechanisms of EGFR overexpression, is highly variable and found in up to 24% of triple-negative breast cancer. 10,11,13,14,19,25 EGFR gene mutation, another mechanism of EGFR overexpression, has been reported to be rare, 11,17,19,25,26 although a recent study reported that it was present in 11% of triplenegative breast cancers. 16 EGFR immunoreactivity has been presented as an independent indicator of poor prognosis in patients with triple-negative breast cancer.…”

Section: Introductionmentioning

confidence: 99%

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High EGFR gene copy number predicts poor outcome in triple-negative breast cancer

Park¹,

et al. 2014

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Epidermal growth factor receptor (EGFR) is frequently overexpressed in triple-negative breast cancer and is emerging as a therapeutic target. EGFR gene copy number alteration and mutation are highly variable and scientists have been challenged to define their prognostic significance in triple-negative breast cancer. We examined EGFR protein expression, EGFR gene copy number alteration and mutation of exon 18 to 21 in 151 cases of triple-negative breast cancer and correlated these findings with clinical outcomes. In addition, intratumoral agreement of EGFR protein overexpression and gene copy number alteration was evaluated. EGFR overexpression was found in 97 of 151 cases (64%) and high EGFR gene copy number was detected in 50 cases (33%), including 3 gene amplification (2%) and 47 high polysomy (31%). Five EGFR mutations were detected in 4 of 151 cases (3%) and included G719A in exon 18 (n ¼ 1), V786M in exon 20 (n ¼ 1), and L858R in exon 21 (n ¼ 3). One case had two mutations (G719A and L858R). High EGFR copy number, but not EGFR mutation, correlated with EGFR protein overexpression. Intratumoral heterogeneity of EGFR protein overexpression and EGFR copy number alteration was not significant. In survival analyses, high EGFR copy number was found to be an independent prognostic factor for poor disease-free survival in patients with triple-negative breast cancer. Our findings showed that EGFR mutation was a rare event, but high EGFR copy number was relatively frequent and correlated with EGFR overexpression in triple-negative breast cancer. Moreover, high EGFR copy number was associated with poor clinical outcome in triple-negative breast cancer, suggesting that evaluation of EGFR copy number may be useful for predicting outcomes in patients with triple-negative breast cancer and for selecting patients for anti-EGFR-targeted therapy.

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Section: Discussioncontrasting

confidence: 72%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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High EGFR gene copy number predicts poor outcome in triple-negative breast cancer

Park¹,

et al. 2014

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Rare oncogenic mutations of predictive markers for targeted therapy in triple-negative breast cancer

Grob

Heilenkötter

Geist³

et al. 2012

Breast Cancer Res Treat

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Women with triple-negative breast cancer (TNBC) do not benefit from endocrine therapy or trastuzumab. Chemotherapy is the only systemic therapy currently available. To reduce the elevated risk of disease progression in these patients, better treatment options are needed, which are less toxic and more targeted to this patient population. We performed a comprehensive analysis of potential targetable genetic aberrations affecting the receptor tyrosine kinase/RAS/MAPK pathway, which are observed at higher frequencies in adenocarcinomas of other organs. Sixty-five individual TNBCs were studied by sequence analysis for HER2 (exon 18-23), EGFR (exon 18-21), KRAS (exon 2), and BRAF (exon 15) mutations. In addition, a tissue microarray was constructed to screen for EGFR gene copy gain and EML4-ALK fusion by FISH. Triple-negative status was confirmed by immunohistochemistry and FISH on tissue microarray sections. EGFR and CK5/6 immunohistochemical analyses were performed for identification of the basal-like phenotype. In addition, mutation analysis of TP53 (exon 5-8) was included. Sequence analysis revealed HER2 gene mutation in only one patient (heterozygous missense mutation in exon 19: p.L755S). No mutations were found in EGFR, KRAS, and BRAF. High polysomy of EGFR was detected in 5 of the 62 informative cases by FISH. True EGFR gene amplification accompanied by strong membranous EGFR protein expression was observed in only one case. No rearrangement of the ALK gene was detected. Basal-like phenotype was identified in 38 of the 65 TNBCs (58.5 %). TP53 gene mutation was found in 36/63 (57.1 %) tumors. We conclude that targetable genetic aberrations in the receptor tyrosine kinase/RAS/MAPK pathway occur rarely in TNBC.

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Determination of HER2 and p53 Mutations by Sequence Analysis Method and EGFR/Chromosome 7 Gene Status by Fluorescence in Situ Hybridization for the Predilection of Targeted Therapy Modalities in Immunohistochemically Triple Negative Breast Carcinomas in Turkish Population

Pala

Bayol

Keskin

et al. 2015

Pathol. Oncol. Res.

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Triple negative breast cancer (TNBC), an agressive subtype accounts nearly 15 % of all breast carcinomas. Conventional chemotherapy is the only treatment modality thus new, effective targeted therapy methods have been investigated. Epidermal growth factor receptor (EGFR) inhibitors give hope according to the recent studies results. Also therapeutic agents have been tried against aberrant p53 signal activity as TNBC show high p53 mutation rates. Our aim was to detect the incidence of mutations/amplifications identified in TNBC in our population. Here we used sequence analysis to detect HER2 (exon 18-23), p53 (exon 5-8) mutations; fluorescence in situ hybridization (FISH) method to analyse EGFR/chromosome 7 centromere gene status in 82 immunohistochemically TNBC. Basaloid phenotype was identified in 49 (59.8 %) patients. EGFR amplification was noted in 5 cases (6.1 %). All EGFR amplified cases showed EGFR overexpression by immunohistochemistry (IHC). p53 mutations were identified in 33 (40.2 %) cases. Almost 60 % of the basal like breast cancer cases showed p53 mutation. Only one case showed HER2 mutation (exon 20:g.36830_3). Our results showed that gene amplification is not the unique mechanism in EGFR overexpression. IHC might be used in the decision of anti-EGFR therapy in routine practice. p53 mutation rate was lower than the rates reported in the literature probably due to ethnic differences and low sensitivity of sanger sequences in general mutation screening. We also established the rarity of HER2 mutation in TNBC. In conclusion EGFR and p53 are the major targets in TNBC also for our population.

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EGFR expression and gene copy number in triple-negative breast carcinoma

Cited by 63 publications

References 27 publications

High EGFR gene copy number predicts poor outcome in triple-negative breast cancer

High EGFR gene copy number predicts poor outcome in triple-negative breast cancer

Rare oncogenic mutations of predictive markers for targeted therapy in triple-negative breast cancer

Determination of HER2 and p53 Mutations by Sequence Analysis Method and EGFR/Chromosome 7 Gene Status by Fluorescence in Situ Hybridization for the Predilection of Targeted Therapy Modalities in Immunohistochemically Triple Negative Breast Carcinomas in Turkish Population

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