The Predictive Value of Pre-therapeutic Serum Gamma-glutamyl transferase in Efficacy and Adverse Reactions to Neoadjuvant Chemotherapy among Breast Cancer Patients

Lu Sun, Wenjin Yin, Ziping Wu, Yaohui Wang, Jinsong Lu, Lu Sun, Wenjin Yin, Ziping Wu, Yaohui Wang, Jinsong Lu

Abstract

Purpose: Gamma-glutamyl transferase (GGT) has been reported as being involved in tumor progression. Previous studies documented a potential relationship between serum GGT level and survival outcome in several types of human malignancies. However, the association between serum GGT levels and response to neoadjuvant chemotherapy (NAC) has not yet been reported. The present study aimed to evaluate the association between pre-therapeutic serum GGT level and the efficacy, long-term survival, and adverse reactions of NAC and to investigate its role in predicting NAC sensitivity in patients with breast cancer.

Methods: A total of 129 patients were recruited and stratified into 2 groups according to serum GGT level (< 29 U/L and ≥ 29 U/L). The association between pre-therapeutic serum GGT levels and clinicopathological parameters was examined. The correlation between pre-therapeutic serum GGT levels and pathological complete response (pCR) was analyzed using univariate and multivariate logistic regression. Survival analyses of relapse-free survival (RFS) and disease-free survival (DFS) were performed. Pearson's χ2 test and multivariate logistic regression model were used to analyze the correlation between pre-therapeutic serum GGT levels and adverse reactions.

Results: Pre-therapeutic serum GGT levels were associated with pCR among breast cancer patients treated with NAC. Multivariate analysis showed that low-level GGT significantly increased pCR rate. Patients in the high-level GGT group had poorer survival than those in the low-level GGT group. Subgroup analysis demonstrated that serum GGT level was potentially related to RFS and DFS in the hormone receptor-positive group. Low levels of GGT are significantly associated with a higher incidence of neutropenia.

Conclusion: Pre-therapeutic serum GGT level is an independent and novel biomarker for predicting the efficiency, prognosis, and adverse reactions to NAC in breast cancer patients. Patients with low pre-therapeutic serum GGT levels are more likely to have higher pCR rates, better RFS and DFS, and higher hematologic toxicity.

Trial registration: ClinicalTrials.gov Identifier: NCT02199418, NCT02221999.

Keywords: Breast cancer; Chemotherapy; Gamma-glutamyltransferase; Neoadjuvant therapy; Prognosis.

Conflict of interest statement

Conflict of Interest: The authors declare that they have no competing interests.

© 2020 Korean Breast Cancer Society.

Figures

Figure 1. Comparison of pCR rate with…
Figure 1. Comparison of pCR rate with pre-therapeutic serum GGT level. The difference of (A) tpCR, (B) bpCR, and (C) near-pCR rate between the low GGT group and the high GGT group were analyzed using the Mann-Whitney test.
GGT, gamma-glutamyl transferase; tpCR, total pathological complete response; bpCR, pathological complete response in breast; pCR, pathological complete response.
Figure 2. Kaplan-Meier curves for relapse-free survival.…
Figure 2. Kaplan-Meier curves for relapse-free survival. Kaplan-Meier survival estimates and log-rank tests were used to analyze the prognostic significance of the pre-therapeutic serum GGT level among (A) HER-2 positive, (B) hormone receptor-positive breast cancer, and (C) all patients treated with neoadjuvant chemotherapy.
GGT, gamma-glutamyl transferase; HER-2, human epidermal growth factor receptor-2.
Figure 3. Kaplan-Meier curves for DFS. Kaplan-Meier…
Figure 3. Kaplan-Meier curves for DFS. Kaplan-Meier survival estimates and log-rank tests were used to analyze the prognostic significance of the pre-therapeutic serum GGT level among (A) all, (B) HER-2 positive, and (C) hormone receptor-positive breast cancer patients treated with neoadjuvant chemotherapy.
GGT, gamma-glutamyl transferase; HER-2, human epidermal growth factor receptor-2; DFS, disease-free survival.

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