Abstract
Triple-negative breast cancer (TNBC) is an aggressive cancer with limited treatment options. Dual specificity phosphatase 4 (DUSP4) has recently been suggested as a potential marker of chemotherapy resistance for TNBC. DUSP4 gene expression levels were measured in breast cancer tissue from 469 TNBC patients aged 20–75 years who participated in the Shanghai Breast Cancer Survival Study, and their association with recurrence/breast cancer mortality and total mortality was evaluated. Information on breast cancer diagnosis, treatment, and disease progression was collected via medical chart review and multiple in-person follow-up surveys. A Cox regression model was applied in the data analyses. Over a median follow-up of 5.3 years (range: 0.7–8.9 years), 100 deaths and 92 recurrences/breast cancer deaths were documented. Expression levels of transcript variant 1 (NM_001394) and transcript variant 2 (NM_057158) of the DUSP4 gene were studied and were highly correlated (r = 0.76). Low DUSP4 expression levels, particularly of variant 1, were associated with both increased recurrence/breast cancer mortality and increased overall mortality. Hazard ratios with adjustment for age at diagnosis and TNM stage associated with below versus above the median expression level were 1.97 (95 % confidence interval (CI): 1.27–3.05) for recurrence/breast cancer mortality and 2.09 (95 % CI: 1.38–3.17) for overall mortality. Additional adjustment for expression levels of MKI67 and TP53, common treatment types, breast cancer subtype, and grade did not materially alter the observed associations. Low DUSP4 expression levels predict recurrence and mortality in TNBC patients independently from known clinical and molecular predictors.
Abbreviations
- DUSP4:
-
Dual specificity phosphatase 4
- TNBC:
-
Triple-negative breast cancer
- ER:
-
Estrogen receptor
- PR:
-
Progesterone receptor
- HER2:
-
Human epidermal growth factor receptor 2
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Acknowledgments
We thank Regina Courtney and Bo Huang for their help with RNA sample preparation. Sample preparation was conducted at the Survey and Biospecimen Shared Resources, which is supported in part by the Vanderbilt-Ingram Cancer Center (P30CA068485). NanoString nCounter assays were conducted at the University of Miami Sylvester Comprehensive Cancer Center. This study was supported by grants from the US Department of Defense (DOD) Breast Cancer Research Program (DAMD 17-02-1-0607 to X.-O. Shu) and the National Institutes of Health (NIH; R01 CA118229 to X.-O. Shu, P50CA098131 to C. Arteaga). Michelle Baglia is funded by a Clinical and Translational Science Award (CTSA) TL1 fellowship.
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This study complies with the current laws of the country in which they were performed.
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The authors have no conflicts of interest to disclose.
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Baglia, M.L., Cai, Q., Zheng, Y. et al. Dual specificity phosphatase 4 gene expression in association with triple-negative breast cancer outcome. Breast Cancer Res Treat 148, 211–220 (2014). https://doi.org/10.1007/s10549-014-3127-z
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DOI: https://doi.org/10.1007/s10549-014-3127-z