MAPK overexpression is associated with anthracycline resistance and increased risk for recurrence in patients with triple-negative breast cancer.
BACKGROUND
Triple-negative breast cancer is estimated to account for 15%-20% of all patients with breast cancer and is considered as a prognostically unfavorable subset. The aim of this study is to evaluate the prognostic impact of various molecular factors in patients with triple-negative breast cancer.


METHODS
Tumor specimens from 109 patients with receptor-negative (estrogen receptor and progesterone receptor) breast cancer were analyzed for mitogen-activated protein kinase (MAPK), epidermal growth factor receptor (EGFR) and phosphoinositol-3-kinase (PI3K) expression by immunohistochemistry. The prognostic significance of these molecular factors, in addition to various prognostic variables, was investigated.


RESULTS
Fifteen (13.8%), 38 (34.9%) and 33 patients (30.3%) had positive staining for EGFR, MAPK and PI3K, respectively. MAPK was associated with anthracycline resistance (P = 0.008) and lower MAPK score was significantly associated with shorter disease-free survival (P = 0.029). Survival following relapse was significantly worse for those with a higher MAPK score (P = 0.03).


CONCLUSIONS
MAPK is a significant prognostic and predictive factor in patients with triple-negative breast cancer. Furthermore, the level of staining among those with a positive MAPK expression may play a prognostic role at different stages of relapse. Further translational research is required to elucidate molecular mechanisms of tumor proliferation in this subset of patients.
Eralp
Y
Y
Department of Medical Oncology, Institute of Oncology, Istanbul University, Topkapi, 34390 Istanbul, Turkey. yeralp@yahoo.com
Derin
D
D
Ozluk
Y
Y
Yavuz
E
E
Guney
N
N
Saip
P
P
Muslumanoglu
M
M
Igci
A
A
Kücücük
S
S
Dincer
M
M
Aydiner
A
A
Topuz
E
E
D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000494:pharmacology* / Q000627:therapeutic use; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000201:enzymology*; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis*; D009364:Neoplasm Recurrence, Local / Q000737:chemistry / Q000201:enzymology*; D016017:Odds Ratio; D019869:Phosphatidylinositol 3-Kinases / Q000032:analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D015854:Up-Regulation
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D014408:Biomarkers, Tumor; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases