title: Activated PI3K/AKT and MAPK pathways are potential good prognostic markers in node-positive, triple-negative breast cancer.
abstract: BACKGROUND
  Triple-negative breast cancer (TNBC) patients are a poor prognostic subgroup, and currently, there is no biomarker for targeted therapy.
  
  
  METHODS
  Tissue samples were obtained from 75 TNBC patients with lymph-node metastases who had received adjuvant chemotherapy. We examined 11 biomarkers, including PIK3CA and AKT1mutation, with regard to event-free survival (EFS) and overall survival (OS) of patients.
  
  
  RESULTS
  In the tumor tissues, phospho-AKT (pAKT) expression was significantly related to HER4 expression. Expression of each of these biomarkers was significantly related to longer EFS (P = 0.024 and 0.03, respectively). pERK expression was also a good prognostic factor regarding EFS and OS in TNBC (P = 0.002 and 0.006, respectively). We also identified a correlation between epidermal growth factor receptor positivity and insulin-like growth factor receptor type 1 positivity (P = 0.001). pERK and T-stage (1-3 versus >3) were independent good prognostic factors by multivariate analysis.
  
  
  CONCLUSIONS
  We determined that tumors expressing pAKT or pERK are a good prognostic subtype in node-positive TNBC. Different targeted therapies may be necessary for TNBC that involves activation of PI3K/AKT or MAPK pathways.
authors.affiliation: Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tsuda
authors.affiliation: Shien-laboratory, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Koizumi
authors.affiliation: Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Shimizu
authors.affiliation: Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yonemori
authors.affiliation: Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ando
authors.affiliation: Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kodaira
authors.affiliation: Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yunokawa
authors.affiliation: Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. Electronic address: ketamura@ncc.go.jp.
authors.forename: K
authors.initials: K
authors.lastname: Tamura
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis* / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D066247:Receptor, ErbB-4 / Q000096:biosynthesis; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*
chemical_list: D014408:Biomarkers, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D066247:Receptor, ErbB-4; C484760:PIK3CA protein, human; C587689:ERBB4 protein, human
keywords: HER4:PI3K; MAPK; biomarkers; prognosis; triple-negative breast cancer