title: Triple negative breast tumors in African-American and Hispanic/Latina women are high in CD44+, low in CD24+, and have loss of PTEN.
abstract: BACKGROUND
  African-American women have higher mortality from breast cancer than other ethnic groups. The association between poor survival and differences with tumor phenotypes is not well understood. The purpose of this study is to assess the clinical significance of (1) Stem cell-like markers CD44 and CD24; (2) PI3K/Akt pathway associated targets PTEN, activation of Akt, and FOXO1; and (3) the Insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP3) in different breast cancer subtypes, and compare the differences between African-American and Hispanic/Latina women who have similar social-economic-status.
  
  
  METHODS
  A total of N=318 African-American and Hispanic/Latina women, with clinically-annotated information within the inclusion criteria were included. Formalin fixed paraffin embedded tissues from these patients were tested for the different markers using immunohistochemistry techniques. Kaplan-Meier survival-curves and Cox-regression analyses were used to assess Relative Risk and Disease-Free-Survival (DFS).
  
  
  RESULTS
  The triple-negative-breast-cancer (TNBC) receptor-subtype was more prevalent among premenopausal women, and the Hormonal Receptor (HR) positive subtype was most common overall. TNBC tumors were more likely to have loss of PTEN, express high Ki67, and have increased CD44+/CD24- expression. TNBC was also associated with higher plasma-IGF-I levels. HR-/HER2+ tumors showed high pAkt, decreased FOXO1, and high CD24+ expression. The loss of PTEN impacted DFS significantly in African Americans, but not in Hispanics/Latinas after adjusted for treatment and other tumor pathological factors. The CD44+/CD24- and CD24+/CD44- phenotypes decreased DFS, but were not independent predictors for DFS. HER2-positive and TNBC type of cancers continued to exhibit significant decrease in DFS after adjusting for the selected biomarkers and treatment.
  
  
  CONCLUSIONS
  TNBC incidence is high among African-American and Hispanic/Latino women residing in South Los Angeles. Our study also shows for the first time that TNBC was significantly associated with PTEN loss, high Ki67 and the CD44+/CD24- phenotype. The loss of PTEN impacts DFS significantly in African Americans.
authors.affiliation: Division of Cancer Research and Training, David Geffen UCLA School of Medicine, Los Angeles, California, United States of America ; Department of Internal Medicine, David Geffen UCLA School of Medicine, Los Angeles, California, United States of America ; Charles R. Drew University of Medicine and Science, David Geffen UCLA School of Medicine, Los Angeles, California, United States of America ; Jonsson Comprehensive Cancer Center and David Geffen UCLA School of Medicine, Los Angeles, California, United States of America.
authors.forename: Yanyuan
authors.initials: Y
authors.lastname: Wu
authors.forename: Marianna
authors.initials: M
authors.lastname: Sarkissyan
authors.forename: Yahya
authors.initials: Y
authors.lastname: Elshimali
authors.forename: Jaydutt V
authors.initials: JV
authors.lastname: Vadgama
mesh_terms: D000328:Adult; D001741:Black or African American; D001943:Breast Neoplasms / Q000208:ethnology / Q000378:metabolism / Q000473:pathology; D051927:CD24 Antigen; D006630:Hispanic or Latino; D006801:Humans; D018960:Hyaluronan Receptors; D015141:Los Angeles; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins; D051059:PTEN Phosphohydrolase
chemical_list: D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human