Association of Dual Specific Phosphatase 4 (DUSP4) Expression and Anthracycline-Based Neoadjuvant Chemotherapy Response in Breast Cancer

Prihantono Prihantono, Mochammad Hatta, Daniel Sampepajung, Andi Asadul Islam, Warsinggih Rahardjo, William Hamdani, Christian Binekada, Haryasena Haryasena, Berti Nelwan

Abstract


Background: Chemotherapy is important component in the management of breast cancer. To achieved better chemotherapy response, a predictive marker is needed. Various studies shows that DUSP4 expression correlates with chemotherapy response. Objectives: Aims of this study is to know association between DUSP4 expression with anthracycline-based neoadjuvant chemotherapy in locally advanced breast cancer. Methods: This is an observational study with longitudinal study method, DUSP4 expression is confirmed with Immunohistochemistry, chemotherapy response is calculated using RECIST criteria. Results: Total sample of this study were 63 breast cancer patients. This study shows that there is a tendency for better chemotherapy response in DUSP4 expression, although it is not statistically significant (p=0.073). Stratification of DUSP4 expression analysis based on intrinsic subtype, DUSP4 expression correlated with luminal B subtype (p=0.024), OR : 2.33 (1.106 - 4.492).

DUSP4 expression on other subtypes were no significantly correlated, luminal A (p=0.245) and Her2 (p=0.612). Conclusion: Overall DUSP4 expression is less associated with chemotherapy response. DUSP4 expression on subtype Luminal B has a significant association with chemotherapy response.


Keywords


Breast Cancer; Chemotherapy; Clinical Response; DUSP4; Intrinsic subtype; Anthracycline.

Full Text:

PDF

References


Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA: a cancer journal for clinicians. 2011;61(2):69-90.

Rhodes A, Yip C. Comparison of breast cancer in Indonesia and Malaysiaa clinico-pathological study between Dharmais Cancer Centre Jakarta and University Malaya Medical Centre, Kuala Lumpur. Asian Pacific Journal of Cancer Prevention. 2011;12:2943-6.

Youlden DR, Cramb SM, Yip CH, Baade PD. Incidence and mortality of female breast cancer in the Asia-Pacific region. Cancer biology & medicine. 2014;11(2):101-15.

Kaufmann M, Hortobagyi GN, Goldhirsch A, Scholl S, Makris A, Valagussa P, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. Journal of Clinical Oncology. 2006;24(12):1940-9.

Connolly RM, Stearns V. Current approaches for neoadjuvant chemotherapy in breast cancer. European journal of pharmacology. 2013;717(1):58-66.

Lee A, Lim W, Moon B-I, Paik N-S, Koh S-H, Song J-Y. Chemotherapy response assay test and prognosis for breast cancer patients who have undergone anthracycline-and taxane-based chemotherapy. Journal of breast cancer. 2011;14(4):283-8.

Press MF, Sauter G, Buyse M, Bernstein L, Guzman R, Santiago A, et al. Alteration of topoisomerase IIalpha gene in human breast cancer: Association with responsiveness to anthracycline-based chemotherapy. Journal of Clinical Oncology. 2011;29(7):859-67.

Liu Y, Du F, Chen W, Yao M, Lv K, Fu P. Knockdown of dual specificity phosphatase 4 enhances the chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin. Experimental cell research. 2013;319(20):3140-9.

Luqmani Y. Mechanisms of drug resistance in cancer chemotherapy. Medical Principles and Practice. 2005;14(Suppl. 1):35-48.

Fountzilas G, Dafni U, Bobos M, Kotoula V, Batistatou A, Xanthakis I, et al. Evaluation of the prognostic role of centromere 17 gain and HER2/topoisomerase II alpha gene status and protein expression in patients with breast cancer treated with anthracycline-containing adjuvant chemotherapy: pooled analysis of two Hellenic Cooperative Oncology Group (HeCOG) phase III trials. BMC cancer. 2013;13(1):1.

Gong C, Yao H, Liu Q, Chen J, Shi J, Su F, et al. Markers of tumor-initiating cells predict chemoresistance in breast cancer. PloS one. 2010;5(12):e15630.

Balko JM, Cook RS, Vaught DB, Kuba MG, Miller TW, Bhola NE, et al. Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance. Nature medicine. 2012;18(7):1052-9.

Smith A, Price C, Cullen M, Muda M, King A, Ozanne B, et al. Chromosomal localization of three human dual specificity phosphatase genes (DUSP4, DUSP6, and DUSP7). Genomics. 1997;42(3):524-7.

Huang C-Y, Tan T-H. DUSPs, to MAP kinases and beyond. Cell & bioscience. 2012;2(1):1.

CAMPS M, Nichols A, Arkinstall S. Dual specificity phosphatases: a gene family for control of MAP kinase function. The FASEB Journal. 2000;14(1):6-16.

Balko JM, Schwarz LJ, Bhola NE, Kurupi R, Owens P, Miller TW, et al. Activation of MAPK pathways due to DUSP4 loss promotes cancer stem cell-like phenotypes in basal-like breast cancer. Cancer research. 2013;73(20):6346-58.

Rottenberg S, Jonkers J. MEK inhibition as a strategy for targeting residual breast cancer cells with low DUSP4 expression. Breast Cancer Research. 2012;14(6):1-2.

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). European journal of cancer. 2009;45(2):228-47.

Kim H, Jang SM, Ahn H, Sim J, Yi K, Chung Y, et al. Clinicopathological Significance of Dual-Specificity Protein Phosphatase 4 Expression in Invasive Ductal Carcinoma of the Breast. Journal of breast cancer. 2015;18(1):1-7.

Sim J, Yi K, Kim H, Ahn H, Chung Y, Rehman A, et al. Immunohistochemical expression of dual-specificity protein phosphatase 4 in patients with colorectal adenocarcinoma. Gastroenterology research and practice. 2015;2015.

Adams J, Cory S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene. 2007;26(9):1324-37.

Armes JE, Hammet F, de Silva M, Ciciulla J, Ramus SJ, Soo W-K, et al. Candidate tumor-suppressor genes on chromosome arm 8p in early-onset and high-grade breast cancers. Oncogene. 2004;23(33):5697-702.

Baglia ML, Cai Q, Zheng Y, Wu J, Su Y, Ye F, et al. Dual specificity phosphatase 4 gene expression in association with triple-negative breast cancer outcome. Breast cancer research and treatment. 2014;148(1):211-20.


Refbacks

  • There are currently no refbacks.


 
 
  
 

 

  


About IJSBAR | Privacy PolicyTerms & Conditions | Contact Us | DisclaimerFAQs 

IJSBAR is published by (GSSRR).