title: Race and triple negative threats to breast cancer survival: a population-based study in Atlanta, GA.
abstract: BACKGROUND
  Breast cancers with a triple negative tumor (TNT) subtype (as defined by lacking protein expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)) preclude the use of available targeted therapies and may contribute to poor outcome and to the historically poorest survival observed among African-American (AA) women. This study examines association of the ER/PR/HER2 subtypes with race and breast cancer survival.
  
  
  METHODS
  Breast tumors from a population-based cohort of 116 AA and 360 white Atlanta women aged 20-54, diagnosed from 1990 to 1992 were centrally reviewed and tested by immunohistochemistry. Multivariate survival analyses within subtypes (TNT, ER-PR-HER2+, ER+/PR+HER2+, ER+/PR+HER2-) were conducted using weighted Cox regression and included socio-demographic, prognostic, and treatment factors.
  
  
  RESULTS
  TNTs were more prevalent among young women and particularly among AA women (Odds Ratio [OR] = 1.9, 95% Confidence Interval [CI] 1.2-2.9), adjusting for age, stage, grade, and poverty index. Overall mortality was higher for AA women (Hazard Ratio [HR] = 1.9, 95% CI, 1.5-2.5) and differed by subtypes (P < 0.001). Within the TNT subtype, racial differences in survival persisted, after additional adjustment for treatment and comorbidities (HR = 2.0, 95% CI 1.0-3.7). TNTs were uniquely associated with high expression of p16, p53, and Cyclin E; and low Bcl-2 and Cyclin D1 expression.
  
  
  CONCLUSIONS
  The high prevalence of TNTs among younger women and particularly younger AA women, along with unique protein expression patterns and poorer survival, suggests varying gene-environment etiologies with respect to age and race/ethnicity and a need for effective therapies.
authors.affiliation: Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Road, NE, Atlanta, GA 30322, USA. mlund@sph.emory.edu
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Lund
authors.forename: Katrina F
authors.initials: KF
authors.lastname: Trivers
authors.forename: Peggy L
authors.initials: PL
authors.lastname: Porter
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Coates
authors.forename: Brian
authors.initials: B
authors.lastname: Leyland-Jones
authors.forename: Otis W
authors.initials: OW
authors.lastname: Brawley
authors.forename: Elaine W
authors.initials: EW
authors.lastname: Flagg
authors.forename: Ruth M
authors.initials: RM
authors.lastname: O'Regan
authors.forename: Sheryl G A
authors.initials: SG
authors.lastname: Gabram
authors.forename: J William
authors.initials: JW
authors.lastname: Eley
mesh_terms: D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data*; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry / Q000208:ethnology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002277:Carcinoma / Q000737:chemistry / Q000208:ethnology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D015331:Cohort Studies; D005260:Female; D005845:Georgia / Q000453:epidemiology; D006801:Humans; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D009363:Neoplasm Proteins / Q000032:analysis*; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012307:Risk Factors; D012959:Socioeconomic Factors; D016019:Survival Analysis; D014505:Urban Population; D044465:White People / Q000706:statistics & numerical data*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone