title: Breast cancer stem cells phenotype and plasma cell-predominant breast cancer independently indicate poor survival.
abstract: OBJECTIVE
  Cancer stem cell-tumor microenvironment ecosystem is proposed to drive tumor heterogeneity. Tumor-infiltrating lymphocytes (TILs) in breast cancer ecosystem were demonstrated to indicate better prognosis and benefit from chemotherapy. This study sought to detect the association between breast cancer stem cells and TILs.
  
  
  METHODS
  92 patients with breast cancer were enrolled. Matched cancerous and paracancerous tissues were assembled in a tissue microarray and immunohistochemistry was employed to test expression of breast cancer stem cells (BCSCs) markers. TILs counts were estimated with global hematoxylin-eosin staining. The association between TILs and BCSCs phenotypes was analysed by multivariate analysis.
  
  
  RESULTS
  Although it was unable to find direct significant association between BCSCs phenotypes and TILs, the BCSCs phenotype with CD44(+)CD24(-)ALDH1A1(+)EpCAM(+)CD49f(+) was proved to be associated with worse DFS and OS (P=0.037 and 0.001). This result was confirmed by cox proportional-hazards regression model (for DFS and OS respectively, HR=2.438 and 3.383, P=0.019 [95%CI 1.418-3.457] and 0.025 [95%CI 1.162-9.843]). Additionally, in results of TILs, plasma cell-predominant breast cancer (PPBC) was unexpectedly found to indicate worse OS and HR was 2.686 (P=0.038 [95%CI 1.582-3.789]).
  
  
  CONCLUSIONS
  The BCSCs phenotype and PPBC may be helpful stratified factors in future clinical trials. The underlying mechanism needs further research.
authors: Breast Center, the Fist Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, Zhejiang Province, 310003 China. Electronic address: whycherry77@hotmail.com.
authors: Haiyan
authors: H
authors: Wei
authors: Breast Center, the Fist Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, Zhejiang Province, 310003 China. Electronic address: peifen_fu@yeah.net.
authors: Peifen
authors: P
authors: Fu
authors: Breast Center, the Fist Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, Zhejiang Province, 310003 China. Electronic address: lionlegend@163.com.
authors: Minya
authors: M
authors: Yao
authors: Breast Center, the Fist Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, Zhejiang Province, 310003 China. Electronic address: wrailly@sina.com.
authors: Yaomin
authors: Y
authors: Chen
authors: Department of Intensive Care Unit, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310009 China. Electronic address: du_linlin2007@163.com.
authors: Linlin
authors: L
authors: Du
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010641:Phenotype; D010950:Plasma Cells / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment
keywords: Breast cancer stem cells (BCSCs); Plasma cells; Prognosis; Tumor microenvironment (TME); Tumor-infiltrating lymphocytes (TILs)