EGFR expression correlates with decreased disease-free survival in triple-negative breast cancer: a retrospective analysis based on a tissue microarray

Liu, Donggen; He, Jiehua; Yuan, Zhongyu; Wang, Shusen; Peng, Roujun; Shi, Yanxia; Teng, Xiaoyu; Qin, Tao

doi:10.1007/s12032-011-9827-x

Cited by 81 publications

(65 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moderate to strong membranous staining in 410% of tumor cells was regarded as EGFR overexpression and was found in 97 (64%) of 151 triple-negative breast cancer cases, comparable to previous studies. However, in contrast to previous studies suggesting prognostic implications of EGFR overexpression in triplenegative breast cancer, 18,20 we did not observe a survival difference associated with EGFR protein expression. This conflicting result may be attributable to differences in the antibodies used and different definitions of EGFR overexpression.…”

Section: Discussioncontrasting

confidence: 99%

“…In this study, high EGFR copy number was significantly associated with poor disease-free survival and acted as an independent poor prognostic factor. Although EGFR overexpression has been presented as a poor prognostic indicator in triplenegative breast cancer, 18,20 high EGFR copy number has no reported prognostic impact in patients with triple-negative breast cancer. The mechanism by which high EGFR copy number contributes to the progression of triple-negative breast cancer is unclear.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11][12][13][14][15][16][17][18][19][20] In this study, we used EGFR pharmDx TM (Dako), which is an approved anti-EGFR antibody for identification of colorectal cancer patients eligible for treatment with cetuximab or panitumumab. Moderate to strong membranous staining in 410% of tumor cells was regarded as EGFR overexpression and was found in 97 (64%) of 151 triple-negative breast cancer cases, comparable to 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%

“…16 EGFR immunoreactivity has been presented as an independent indicator of poor prognosis in patients with triple-negative breast cancer. 18,20 However, there have been no reports on the prognostic impact of EGFR copy number alteration or mutation in triple-negative breast cancer. Intratumoral heterogeneity of EGFR protein overexpression and copy number alteration has also not been studied in triple-negative breast cancer, although it may be associated with responsiveness to EGFR-targeted therapy.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

Park¹,

et al. 2014

View full text Add to dashboard Cite

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.

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Park¹,

et al. 2014

View full text Add to dashboard Cite

show abstract

Triple Negative Breast Cancer: Nanosolutions for a Big Challenge

2015

View full text Add to dashboard Cite

Triple negative breast cancer (TNBC) is a particular immunopathological subtype of breast cancer that lacks expression of estrogen and progesterone receptors (ER/PR) and amplification of the human epidermal growth factor receptor 2 (HER2) gene. Characterized by aggressive and metastatic phenotypes and high rates of relapse, TNBC is the only breast cancer subgroup still lacking effective therapeutic options, thus presenting the worst prognosis. The development of targeted therapies, as well as early diagnosis methods, is vital to ensure an adequate and timely therapeutic intervention in patients with TNBC. This review intends to discuss potentially emerging approaches for the diagnosis and treatment of TNBC patients, with a special focus on nano‐based solutions that actively target these particular tumors.

show abstract

PLA2G7 associates with hormone receptor negativity in clinical breast cancer samples and regulates epithelial‐mesenchymal transition in cultured breast cancer cells

Lehtinen

Vainio

Wikman

et al. 2017

The Journal of Pathology CR

View full text Add to dashboard Cite

Breast cancer is the leading cause of cancer‐related deaths in women due to distinct cancer subtypes associated with early recurrence and aggressive metastatic progression. High lipoprotein‐associated phospholipase A2 (PLA2G7) expression has previously been associated with aggressive disease and metastasis in prostate cancer. Here, we explore the expression pattern and functional role of PLA2G7 in breast cancer. First, a bioinformatic analysis of genome‐wide gene expression data from 970 breast samples was carried out to evaluate the expression pattern of PLA2G7 mRNA in breast cancer. Second, the expression profile of PLA2G7 was studied in 1042 breast cancer samples including 89 matched lymph node metastasis samples using immunohistochemistry. Third, the effect of PLA2G7 silencing on genome‐wide gene expression profile was studied and validated in cultured breast cancer cells expressing PLA2G7 at high level. Last, the expression pattern of PLA2G7 mRNA was investigated in 24 nonmalignant tissue samples and 65 primary and 7 metastatic tumour samples derived from various organs using qRT‐PCR. The results from clinical breast cancer samples indicated that PLA2G7 is overexpressed in a subset of breast cancer samples compared to its expression in benign breast tissue samples and that high PLA2G7 expression associated with hormone receptor negativity as well as with poor prognosis in a subset of breast cancer samples. In vitro functional studies highlighted the putative role of PLA2G7 in the regulation of epithelial‐mesenchymal transition (EMT)‐related signalling pathways, vimentin and E‐cadherin protein expression as well as cell migration in cultured breast cancer cells. Furthermore, supporting the findings in breast and prostate cancer, high PLA2G7 mRNA expression was associated with metastatic cancer in four additional organs of origin. In conclusion, our results indicate that PLA2G7 is highly expressed in a subset of metastatic and aggressive breast cancers and in metastatic samples of various tissues of origin and promotes EMT and migration in cultured breast cancer cells.

show abstract

EGFR expression correlates with decreased disease-free survival in triple-negative breast cancer: a retrospective analysis based on a tissue microarray

Cited by 81 publications

References 19 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

Triple Negative Breast Cancer: Nanosolutions for a Big Challenge

PLA2G7 associates with hormone receptor negativity in clinical breast cancer samples and regulates epithelial‐mesenchymal transition in cultured breast cancer cells

Contact Info

Product

Resources

About