Expression of T-Lymphocyte Markers in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer

이창로; 박세호; 김주흥; 임성묵; 박형석; 김승일; 박병우

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자료유형: 학술저널

저자정보: 이창로 (연세대학교) 박세호 (연세대학교) 김주흥 (연세대학교) 임성묵 (연세대학교) 박형석 (연세대학교) 김승일 (연세대학교) 박병우 (연세대학교)

저널정보: 한국유방암학회 Journal of Breast Cancer Journal of Breast Cancer Vol.19 No.4

발행연도: 2016.1

수록면: 385 - 393 (9page)

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Purpose: The present study aimed to examine the clinical implications of CD4, CD8, and FOXP3 expression on the prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer using a web-based database, and to compare the immunohistochemical expression of T-lymphocyte markers using primary and metastatic HER2-positive tumor tissues before and after HER2-targeted therapy. Methods: Using the cBioPortal for Cancer Genomics and Kaplan-Meier plotter, the mRNA expression, association between T-lymphocyte markers, and survival in HER2-positive cancers were investigated according to various cutoff levels. Immunohistochemistry analysis was performed using paired primary and metastatic tissues of 29 HER2- positive tumors treated with systemic chemotherapy and HER2- directed therapy. Results: HER2 mRNA was mutually exclusive of T-lymphocyte markers, and a significant correlation between Tcell markers was observed in the cBioPortal for Cancer Genomics. According to analysis of the Kaplan-Meier plotter, the impact of T-lymphocyte marker expression on survival was statistically insignificant in clinical HER2-positive tumors, irrespective of the cutoff levels. However, in the intrinsic HER2-positive subtype, the individual analyses of T-cell markers except for FOXP3 and combined analysis showed significantly favorable survival irrespective of cutoff points. Although the small clinical sample size made it difficult to show the statistical relevance of immunohistochemistry findings, good responses to neoadjuvant treatments might be associated with positive expression of combined T-lymphocyte markers, and approximately half of the samples showed discordance of combined markers between baseline and resistant tumors. Conclusion: T-lymphocyte markers could be favorable prognostic factors in HER2-positive breast cancers; however, a consensus on patient section criteria, detection methods, and cutoff value could not be reached. The resistance to HER2-directed therapy might involve different and personalized mechanisms, and further research is required to understand the association between immune function and HER2 expression and to overcome the resistance mechanisms to HER2-targeted therapies.

참고문헌 (26)

참고문헌 신청

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Slamon DJ / 2001 / Use of chemotherapy plus a monoclonal antibody against HER2for metastatic breast cancer that overexpresses HER2 / N Engl J Med 344:783~792

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