Expression of growth factor and chemokine receptors: new insights in the biology of inflammatory breast cancer

Cabıoğlu, Neslihan; Gong, Yun; Islam, Rabiul; Broglio, Kristine; Sneige, Nour; Şahin, Ayşegül; González-Angulo, Ana M.; Morandi, Paolo; Bucana, C. D.; Hortobágyi, G. N.; Cristofanilli, Massimo

doi:10.1093/annonc/mdm060

Cited by 140 publications

(115 citation statements)

References 43 publications

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“…Indeed, factors such as increased expression of EGFR and p53 and loss of p27 have been shown to be significantly associated with worse outcomes in patients with IBC. 13,11 Another possible explanation is that HER-2-positive tumors often coexpress topoisomerase II, the target of anthracyclines. 25 Because all patients received an anthracycline-containing regimen, this regimen might have been more effective in HER-2-positive tumors than in HER-2-negative tumors and in that manner might have eliminated the impact of HER-2 status in determining RFS.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of HER‐2 status in women with inflammatory breast cancer

Dawood

Broglio

Gong

et al. 2008

Cancer

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BACKGROUND Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer with poorly understood prognostic variables. The purpose of this study was to define the prognostic impact of HER‐2 status on survival outcomes of patients with IBC. METHODS In all, 179 patients with IBC, diagnosed between 1989 and 2005, with known HER‐2 status, and treated with an anthracycline‐based chemotherapy regimen without trastuzumab, were included in the analysis. Patients with HER‐2‐positive disease who received trastuzumab at the time of disease recurrence were included. Survival outcomes were estimated by the Kaplan‐Meier product limit method and compared across groups using the log‐rank statistic. A Cox proportional hazards model was fitted to determine the association of survival outcomes with HER‐2 status after adjusting for patient and tumor characteristics. RESULTS A total of 111 patients (62%) had HER‐2‐negative disease and 68 (38%) had HER‐2‐positive disease. The median follow‐up among all patients was 35 months. At the time of the analysis, 62 patients (55.9%) with HER‐2‐negative disease and 42 patients (61.8%) with HER‐2‐positive disease had a recurrence. Thirty‐one patients (73.8%) with HER‐2‐positive disease who had a disease recurrence went on to receive trastuzumab. On univariate analysis, no statistically significant difference was observed for either recurrence‐free survival (P = .75) or overall survival (P = .24) between patients who had HER‐2‐positive disease and those who had HER‐2‐negative disease. In a multivariate model, HER‐2 status did not appear to significantly affect recurrence‐free survival (hazards ratio [HR] of 0.75; 95% confidence interval [95% CI], 0.46–1.22 [P = .241]). In the multivariate model, patients with HER‐2‐positive disease had a decreased hazard of death (HR of 0.56; 95% CI, 0.34–0.93 [P = .024]) compared with patients with HER‐2‐negative disease. CONCLUSIONS HER‐2 status, in the absence of trastuzumab, did not appear to significantly affect recurrence‐free survival. After adjusting for other characteristics, the addition of trastuzumab in the metastatic setting significantly improved survival in the HER‐2‐positive group above and beyond that of the HER‐2‐negative group. This gives us further insight into the biology of this aggressive disease and underlines the major effect of targeted intervention. Cancer 2008. © 2008 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Prognostic significance of HER‐2 status in women with inflammatory breast cancer

Dawood

Broglio

Gong

et al. 2008

Cancer

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“…The high level of CXCR4 mRNA in tumor cells is believed to be involved in their survival under hypoxia [28]. Further, overexpression of CXCR4 has been associated with metastases formation and poor prognosis of patients with breast and other types of cancer [29][30][31], which explains the significant interest towards CXCR4 inhibitors [32,33].…”

Section: Discussionmentioning

confidence: 99%

Changes in gene expression of CXCR4, CCR7 and BCL2 after treatment of breast cancer cells with saponin extract from Tribulus terrestris

Goranova¹,

Ss²,

Vs³

et al. 2015

neo

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Saponins are natural substances produced by a large number of plants, one of which is Tribulus terrestris L. (TT). They have been reported to possess an antitumor activity exerted by regulating various signaling pathways in the cell. Although the mechanisms of action of saponin extracts from various plants have been widely studied, limited data are available about TT. The present study aimed to analyze the impact of saponin extract from TT on cell processes in breast carcinoma cell lines. The variations in expression of a group of 32 selected genes were examined by real-time PCR after saponin treatment of MCF7 and MCF10A cell lines. Only three genes -CXCR4, CCR7 and BCL2, showed changes in their mRNA levels after the application of the herb extract. While CXCR4 expression was reduced in both cell lines, CCR7 and BCL2 levels decreased only in tumorigenic MCF7 cells, implying cell-specificity of the saponin action. Our results suggested that TT extract containing saponins was likely to affect the processes of apoptosis and metastasizing of cancer cells. Further in vivo studies will show its applicability as an anticancer therapeutic agent.

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“…There are several possible explanations for why HER2 is not prognostic for survival in IBC. Many other molecules may contribute to IBC's aggressive behavior, including chemokine receptors such as CCR7 (Cabioglu et al, 2007), EGFR (Cabioglu et al, 2007), E-cadherin (Colpaert et al, 2003), Rho proteins, and WISP3 (Van Golen et al, 2000;Kleer et al, 2002). Future studies should attempt to identify which molecular target was specific to IBC.…”

Section: Discussionmentioning

confidence: 99%

Lack of Prognostic Value of Human Epidermal Growth Factor- Like Receptor 2 Status in Inflammatory Breast Cancer (IBC): a Meta-analysis

Zha²,

Xu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer which is more likely to be her-2/ neu amplified. While the her-2/neu status has been utilised to predict prognosis, the published data are inconsistent. The present meta-analysis was conducted to determine whether the her-2/neu status predicts outcomes. Papers were selected from the PubMed database based on defined inclusion and exclusion criteria. Parameters such as total patients, follow-up time and outcome statistics (i.e. overall survival (OS), relapse-free survival (RFS) were collected. The analysis included 6 studies with 2,838 IBC patients. The summary hazards ratio (HR) estimating the association of OS with HER-2-positive disease was 0.96 (95% confidence interval (95%CI: 0.85-1.10)), with similar findings for RFS (HR=0.81, 95%CI: 0.61-1.09). No obvious statistical heterogeneity was detected. This meta-analysis suggests that HER-2-positive status is not an independent adverse prognostic factor for survival among IBC patient cases.

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Expression of growth factor and chemokine receptors: new insights in the biology of inflammatory breast cancer

Abstract: These data demonstrate the expression of growth factor and chemokine receptors in IBC. The expression of these receptors is associated with increased risk of recurrence and death, and thus, they may represent potential therapeutic targets in IBC.

Cited by 140 publications

References 43 publications

Prognostic significance of HER‐2 status in women with inflammatory breast cancer

Prognostic significance of HER‐2 status in women with inflammatory breast cancer

Changes in gene expression of CXCR4, CCR7 and BCL2 after treatment of breast cancer cells with saponin extract from Tribulus terrestris

Lack of Prognostic Value of Human Epidermal Growth Factor- Like Receptor 2 Status in Inflammatory Breast Cancer (IBC): a Meta-analysis

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