title: Prognostic evaluation of the B cell/IL-8 metagene in different intrinsic breast cancer subtypes.
abstract: We recently reported that a ratio of high B cell and low IL-8 metagene expression identified 32 % of triple negative breast cancers (TNBC) with good prognosis and was the only significant predictor in multivariate analysis including routine clinicopathological variables. However, the clinical relevance of this signature in other breast cancer subtypes remains unclear. We compiled Affymetrix gene expression datasets from 4,467 primary breast cancer samples and excluded 329 triple negative samples which were used as discovery cohort in our previous study. Molecular classification of the remaining 4,138 samples was performed by two methods, including single genes (ER, PgR, HER2, and Ki67) and a centroid-based method using the intrinsic gene list. The prognostic value within the respective subtypes was assessed by analyzing the event-free survival of patients as a function of the B cell/IL-8 metagene ratio using previously published cutoff. ER-negative subtypes had the highest expression of the B cell and the IL-8 metagenes. The IL-8/B cell signature assigned a considerable fraction of samples (range 20.7-42.0 %) into the "good prognosis" group. However, a significant prognostic value was only observed in the subgroup of triple negative breast cancer (P = 0.035). The prognostic value of the B cell/IL-8 ratio is mainly confined to the basal-like and TNBC subtypes of breast cancer. This result underlines the importance of subtype-specific analyses and suggests a sequential multistep approach to developing and applying outcome predictors in the clinic.
authors.affiliation: Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
authors.forename: Lars C
authors.initials: LC
authors.lastname: Hanker
authors.forename: Achim
authors.initials: A
authors.lastname: Rody
authors.forename: Uwe
authors.initials: U
authors.lastname: Holtrich
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
authors.forename: Eugen
authors.initials: E
authors.lastname: Ruckhaeberle
authors.forename: Cornelia
authors.initials: C
authors.lastname: Liedtke
authors.forename: Andre
authors.initials: A
authors.lastname: Ahr
authors.forename: Tomas M
authors.initials: TM
authors.lastname: Heinrich
authors.forename: Nicole
authors.initials: N
authors.lastname: Sänger
authors.forename: Sven
authors.initials: S
authors.lastname: Becker
authors.forename: Thomas
authors.initials: T
authors.lastname: Karn
mesh_terms: D001402:B-Lymphocytes / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D016209:Interleukin-8; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human