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Elevated levels of chemokine receptor CXCR4 in HER-2 negative breast cancer specimens predict recurrence.
J Surg Res. 2007 Jul; 141(1):53-9.JS

Abstract

INTRODUCTION

CXCR4 is a chemokine receptor that has recently been implicated to play a pivotal role in breast cancer growth and metastasis. In animal models, reduction of CXCR4 expression significantly abrogated metastatic disease and prolonged survival. In human breast cancers, CXCR4 overexpression may portend a worse clinical course. Recent data suggest that HER-2 up-regulates CXCR4, but whether this is applicable in the clinical setting is not known. In this study, we evaluated the role of CXCR4 overexpression in breast cancer and determined whether it can serve as a potential marker of tumor recurrence in HER-2 negative tumors.

METHODS

One hundred three patients with stages I to III breast cancers and 6 benign breast tissues were prospectively accrued and analyzed. Study homogeneity was maintained by standardized treatment, surveillance, and compliance protocols. CXCR4 levels were detected using Western blots and results were quantified against 1 microg of HeLa cells (positive controls). HER-2 expression was evaluated using the Hercep program, (Dako Corp., Carpinteria, CA) with a positive result defined as > or = 2. CXCR4 expression was defined as low (<6.6-fold) or high (> or = 6.6-fold). Primary endpoints were cancer recurrence and death. Statistical analysis performed included Spearman's correlation, independent samples t-test, Kaplan-Meier survival analysis, and log-rank test.

RESULTS

All 103 cancer specimens had CXCR4 overexpression (mean 6.6 +/- 4.7), while none of the 6 benign breast tissues had detectable level of CXCR4. There were 36 HER-2 (+) tumors and 67 HER-2 (-) tumors. There was no statistical significance in mean CXCR4 overexpression between HER-2 (+) [5.6] and HER-2 (-) [6.6] cancers (P = 0.3; independent samples t-test). Recurrences occurred in 18 of 103 patients (17%); 10 occurred in HER-2 (+) tumors, and 8 occurred in HER-2 (-) patients. CXCR4 expression level was not predictive of cancer recurrence (P = 0.80) or overall survival (P = 0.70) in the HER-2 (+) group. However, among HER-2 negative tumors, 7 of 8 recurrences occurred in the high CXCR4 group (P = 0.037). There was no correlation between the degree of CXCR4 overexpression with tumor size (r = 0.13, P = 0.22), nodal status (r = 0.019, P = 0.4), ER/PR status (r = 0.12, P = 0.29), and HER-2 status (r = 0.091, P = 0.36).

CONCLUSIONS

CXCR4 overexpression was observed in all 103 breast cancer specimens but was undetectable in benign breast tissues. CXCR4 overexpression does not correlate with tumor size, nodal status, ER/PR status, and HER-2 status. High CXCR4 overexpression had a significant impact on disease-free survival in HER-2 negative breast cancer patients and may help identify a subset of HER-2 negative breast cancers that have a more aggressive biological behavior.

Authors+Show Affiliations

Department of Surgery, Louisiana State University Health Sciences Center in Shreveport, Shreveport, Louisiana, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17574038

Citation

Holm, Neal T., et al. "Elevated Levels of Chemokine Receptor CXCR4 in HER-2 Negative Breast Cancer Specimens Predict Recurrence." The Journal of Surgical Research, vol. 141, no. 1, 2007, pp. 53-9.
Holm NT, Byrnes K, Li BD, et al. Elevated levels of chemokine receptor CXCR4 in HER-2 negative breast cancer specimens predict recurrence. J Surg Res. 2007;141(1):53-9.
Holm, N. T., Byrnes, K., Li, B. D., Turnage, R. H., Abreo, F., Mathis, J. M., & Chu, Q. D. (2007). Elevated levels of chemokine receptor CXCR4 in HER-2 negative breast cancer specimens predict recurrence. The Journal of Surgical Research, 141(1), 53-9.
Holm NT, et al. Elevated Levels of Chemokine Receptor CXCR4 in HER-2 Negative Breast Cancer Specimens Predict Recurrence. J Surg Res. 2007;141(1):53-9. PubMed PMID: 17574038.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Elevated levels of chemokine receptor CXCR4 in HER-2 negative breast cancer specimens predict recurrence. AU - Holm,Neal T, AU - Byrnes,Kerry, AU - Li,Benjamin D L, AU - Turnage,Richard H, AU - Abreo,Fleurette, AU - Mathis,James M, AU - Chu,Quyen D, PY - 2007/01/08/received PY - 2007/03/13/revised PY - 2007/03/13/accepted PY - 2007/6/19/pubmed PY - 2007/8/10/medline PY - 2007/6/19/entrez SP - 53 EP - 9 JF - The Journal of surgical research JO - J Surg Res VL - 141 IS - 1 N2 - INTRODUCTION: CXCR4 is a chemokine receptor that has recently been implicated to play a pivotal role in breast cancer growth and metastasis. In animal models, reduction of CXCR4 expression significantly abrogated metastatic disease and prolonged survival. In human breast cancers, CXCR4 overexpression may portend a worse clinical course. Recent data suggest that HER-2 up-regulates CXCR4, but whether this is applicable in the clinical setting is not known. In this study, we evaluated the role of CXCR4 overexpression in breast cancer and determined whether it can serve as a potential marker of tumor recurrence in HER-2 negative tumors. METHODS: One hundred three patients with stages I to III breast cancers and 6 benign breast tissues were prospectively accrued and analyzed. Study homogeneity was maintained by standardized treatment, surveillance, and compliance protocols. CXCR4 levels were detected using Western blots and results were quantified against 1 microg of HeLa cells (positive controls). HER-2 expression was evaluated using the Hercep program, (Dako Corp., Carpinteria, CA) with a positive result defined as > or = 2. CXCR4 expression was defined as low (<6.6-fold) or high (> or = 6.6-fold). Primary endpoints were cancer recurrence and death. Statistical analysis performed included Spearman's correlation, independent samples t-test, Kaplan-Meier survival analysis, and log-rank test. RESULTS: All 103 cancer specimens had CXCR4 overexpression (mean 6.6 +/- 4.7), while none of the 6 benign breast tissues had detectable level of CXCR4. There were 36 HER-2 (+) tumors and 67 HER-2 (-) tumors. There was no statistical significance in mean CXCR4 overexpression between HER-2 (+) [5.6] and HER-2 (-) [6.6] cancers (P = 0.3; independent samples t-test). Recurrences occurred in 18 of 103 patients (17%); 10 occurred in HER-2 (+) tumors, and 8 occurred in HER-2 (-) patients. CXCR4 expression level was not predictive of cancer recurrence (P = 0.80) or overall survival (P = 0.70) in the HER-2 (+) group. However, among HER-2 negative tumors, 7 of 8 recurrences occurred in the high CXCR4 group (P = 0.037). There was no correlation between the degree of CXCR4 overexpression with tumor size (r = 0.13, P = 0.22), nodal status (r = 0.019, P = 0.4), ER/PR status (r = 0.12, P = 0.29), and HER-2 status (r = 0.091, P = 0.36). CONCLUSIONS: CXCR4 overexpression was observed in all 103 breast cancer specimens but was undetectable in benign breast tissues. CXCR4 overexpression does not correlate with tumor size, nodal status, ER/PR status, and HER-2 status. High CXCR4 overexpression had a significant impact on disease-free survival in HER-2 negative breast cancer patients and may help identify a subset of HER-2 negative breast cancers that have a more aggressive biological behavior. SN - 0022-4804 UR - https://www.unboundmedicine.com/medline/citation/17574038/Elevated_levels_of_chemokine_receptor_CXCR4_in_HER_2_negative_breast_cancer_specimens_predict_recurrence_ DB - PRIME DP - Unbound Medicine ER -