Elevated Levels of Chemokine Receptor CXCR4 in HER-2 Negative Breast Cancer Specimens Predict Recurrence

Holm, Neal; Byrnes, Kerry; Li, Benjamin D.L.; Turnage, Richard H.; Abreo, Fleurette; Mathis, J. Michael; Chu, Quyen D.

doi:10.1016/j.jss.2007.03.015

Cited by 54 publications

(48 citation statements)

References 25 publications

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“…We recently demonstrated its clinical utility in patients with HER-2-negative tumors, mainly in primary tumors indicating a poor outcome, independent of HER-2 status, ER/PR status, and nodal status (33). As an extension of this study, we evaluated the prognostic significance of S-TK1 in patients with LABC who received neoadjuvant chemotherapy.…”

Section: Discussionmentioning

confidence: 96%

Elevated thymidine kinase 1 in serum following neoadjuvant chemotherapy predicts poor outcome for patients with locally advanced breast cancer

Huang

Tian

Li³

et al. 2011

Experimental and Therapeutic Medicine

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Abstract.Patients with locally advanced breast cancer (LABC) commonly have an unfavorable prognosis. A molecular predictor for the identification of at-risk patients is urgently required. Thymidine kinase 1 in serum (S-TK1) is an enzyme involved in the synthesis of DNA precursors. In studies using immunohistochemistry, it was reported to be a more useful proliferation marker than Ki-67 in breast, lung and colorectal carcinoma. In the present study, we extended the research of prior breast carcinoma studies by postulating that in patients with LABC, overexpression of S-TK1 following neoadjuvant chemotherapy predicts cancer outcome. An experimental design consisting of 48 patients with LABC was prospectively constructed and analyzed. All patients received neoadjuvant chemotherapy and definitive surgical therapy. Study homogeneity was maintained by standardized treatment, surveillance and compliance protocols. The S-TK1 concentration was detected using the anti-TK1 chicken IgY antibody, using a dot-blot immuno-assay. After a median follow-up of 30 months, the results indicated a statistically significant trend (unadjusted). Patients with high S-TK1 overexpression had a significantly higher incidence of recurrence (P= 0.006) and cancer death (P= 0.0128) than those with low S-TK1 overexpression. A multivariate analysis provided identical results. The hazards ratio for developing recurrence in patients with higher S-TK1 expression was 6-7 times higher than the hazards ratio in patients with lower expression. In conclusion, our results indicate that a high S-TK1 concentration in sera from LABC patients receiving neoadjuvant chemotherapy is predictive of cancer outcome.

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Section: Discussionmentioning

confidence: 96%

Elevated thymidine kinase 1 in serum following neoadjuvant chemotherapy predicts poor outcome for patients with locally advanced breast cancer

Huang

Tian

Li³

et al. 2011

Experimental and Therapeutic Medicine

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“…Receptor CXCR4 was overexpressed in HER2-negative breast cancer patients and was correlated with disease-free survival. This was not the case in HER2-positive breast cancer patients, suggesting that receptor CXCR4 may be used to distinguish between patients with long- and short-term survival (21). In a previous study, we demonstrated that HER2 overexpression was associated with significantly higher STK1p values prior to neoadjuvant chemotherapy (22).…”

Section: Discussionmentioning

confidence: 99%

Serum thymidine kinase 1 levels predict cancer-free survival following neoadjuvant, surgical and adjuvant treatment of patients with locally advanced breast cancer

Chen

Tang

Xia

et al. 2013

Molecular and Clinical Oncology

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In this study, the use of serum thymidine kinase 1 protein (STK1p) concentration for the prognosis of the overall survival of patients with locally advanced breast cancer (n=51) following routine treatment (neoadjuvant treatment, surgery and chemotherapy) was investigated. The patients were followed up for 44 months and the STK1p values were determined by a high-sensitivity enhanced chemiluminescence (ECL) dot blot assay. The variables investigated in relation to metastasis and survival were STK1p, clinical stage, tumor size and age, by the Kaplan-Meier method, the log-rank test and Cox uni- and multivariate analyses. Patients with high STK1p values (≥2.0 pM) 3–6 months after surgery exhibited a positive correlation to clinical stage, tumor size, occurrence of metastasis and survival. The hazard risk for the development of metastatic disease and mortality among breast cancer patients was 11–12 times higher in patients with high compared to those with low STK1p values (<2.0 pM). Notably, patients with stage III/IV disease and low STK1p values exhibited statistically significantly improved survival compared to patients with high STK1p values. A multivariate Cox analysis demonstrated that the STK1p levels 6 months after surgery was the only independent prognostic factor for metastasis and survival. In conclusion, STK1p is a prognostic marker in patients with locally advanced breast cancer and it may help identify a subgroup of stage III/IV patients with improved cancer-free survival expectancy, enabling personalized treatment.

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“…CXCR4 is also involved in the metastasis of prostate cancer to the bone marrow (18) and of colon cancer to the liver (19). CXCR4 expression has been correlated with poor overall survival rate in patients with breast cancer (20) and colon cancer (21). Thus, CXCR4 is viewed as a probable therapeutic target for preventing cancer metastasis.…”

Section: Introductionmentioning

confidence: 99%

Zerumbone Down-regulates Chemokine Receptor CXCR4 Expression Leading to Inhibition of CXCL12-Induced Invasion of Breast and Pancreatic Tumor Cells

et al. 2008

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CXC chemokine receptor 4 (CXCR4), initially linked with leukocyte trafficking, is now known to be expressed in various tumors including breast, ovary, prostate, gastrointestinal, head and neck, bladder, brain, and melanoma. This receptor mediates homing of tumor cells to specific organs that express the ligand CXCL12 for this receptor. Thus, agents that can down-regulate CXCR4 expression have potential against cancer metastasis. In this study, we report the identification of zerumbone, a component of subtropical ginger (Zingiber zerumbet), as a regulator of CXCR4 expression. This sesquiterpene down-regulated the expression of CXCR4 on HER2-overexpressing breast cancer cells in a dose-and time-dependent manner. The decrease in CXCR4 by zerumbone was found to be not cell type specific as its expression was abrogated in leukemic, skin, kidney, lung, and pancreatic cancer cell lines. The down-regulation of CXCR4 was not due to proteolytic degradation but rather to transcriptional regulation, as indicated by down-regulation of mRNA expression, inhibition of nuclear factor-KB activity, and suppression of chromatin immunoprecipitation activity. Suppression of CXCR4 expression by zerumbone correlated with the inhibition of CXCL12-induced invasion of both breast and pancreatic cancer cells. An analogue of zerumbone, A-humulene, which lacks the carbonyl group, was found to be inactive in inducing CXCR4 downregulation. Overall, our results show that zerumbone is a novel inhibitor of CXCR4 expression and thus has a potential in the suppression of cancer metastasis. [Cancer Res 2008;68(21):8938-44]

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Elevated Levels of Chemokine Receptor CXCR4 in HER-2 Negative Breast Cancer Specimens Predict Recurrence

Cited by 54 publications

References 25 publications

Elevated thymidine kinase 1 in serum following neoadjuvant chemotherapy predicts poor outcome for patients with locally advanced breast cancer

Elevated thymidine kinase 1 in serum following neoadjuvant chemotherapy predicts poor outcome for patients with locally advanced breast cancer

Serum thymidine kinase 1 levels predict cancer-free survival following neoadjuvant, surgical and adjuvant treatment of patients with locally advanced breast cancer

Zerumbone Down-regulates Chemokine Receptor CXCR4 Expression Leading to Inhibition of CXCL12-Induced Invasion of Breast and Pancreatic Tumor Cells

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