title: A clinically relevant gene signature in triple negative and basal-like breast cancer.
abstract: BACKGROUND
  Current prognostic gene expression profiles for breast cancer mainly reflect proliferation status and are most useful in ER-positive cancers. Triple negative breast cancers (TNBC) are clinically heterogeneous and prognostic markers and biology-based therapies are needed to better treat this disease.
  
  
  METHODS
  We assembled Affymetrix gene expression data for 579 TNBC and performed unsupervised analysis to define metagenes that distinguish molecular subsets within TNBC. We used n = 394 cases for discovery and n = 185 cases for validation. Sixteen metagenes emerged that identified basal-like, apocrine and claudin-low molecular subtypes, or reflected various non-neoplastic cell populations, including immune cells, blood, adipocytes, stroma, angiogenesis and inflammation within the cancer. The expressions of these metagenes were correlated with survival and multivariate analysis was performed, including routine clinical and pathological variables.
  
  
  RESULTS
  Seventy-three percent of TNBC displayed basal-like molecular subtype that correlated with high histological grade and younger age. Survival of basal-like TNBC was not different from non basal-like TNBC. High expression of immune cell metagenes was associated with good and high expression of inflammation and angiogenesis-related metagenes were associated with poor prognosis. A ratio of high B-cell and low IL-8 metagenes identified 32% of TNBC with good prognosis (hazard ratio (HR) 0.37, 95% CI 0.22 to 0.61; P < 0.001) and was the only significant predictor in multivariate analysis including routine clinicopathological variables.
  
  
  CONCLUSIONS
  We describe a ratio of high B-cell presence and low IL-8 activity as a powerful new prognostic marker for TNBC. Inhibition of the IL-8 pathway also represents an attractive novel therapeutic target for this disease.
authors: Department of Obstetrics and Gynecology, J W Goethe-University, Theodor-Stern-Kai 7, Frankfurt, 60590, Germany.
authors: Achim
authors: A
authors: Rody
authors: Thomas
authors: T
authors: Karn
authors: Cornelia
authors: C
authors: Liedtke
authors: Lajos
authors: L
authors: Pusztai
authors: Eugen
authors: E
authors: Ruckhaeberle
authors: Lars
authors: L
authors: Hanker
authors: Regine
authors: R
authors: Gaetje
authors: Christine
authors: C
authors: Solbach
authors: Andre
authors: A
authors: Ahr
authors: Dirk
authors: D
authors: Metzler
authors: Marcus
authors: M
authors: Schmidt
authors: Volkmar
authors: V
authors: Müller
authors: Uwe
authors: U
authors: Holtrich
authors: Manfred
authors: M
authors: Kaufmann
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000473:pathology / Q000502:physiology; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D018295:Neoplasms, Basal Cell / Q000235:genetics / Q000473:pathology; D011237:Predictive Value of Tests; D015996:Survival Rate; D059467:Transcriptome
chemical_list: D016209:Interleukin-8