title: A breast cancer meta-analysis of two expression measures of chromosomal instability reveals a relationship with younger age at diagnosis and high risk histopathological variables.
abstract: Breast cancer in younger patients often presents with adverse histopathological features, including increased frequency of estrogen receptor negative and lymph node positive disease status. Chromosomal instability (CIN) is increasingly recognised as an important prognostic variable in solid tumours. In a breast cancer meta-analysis of 2423 patients we examine the relationship between clinicopathological parameters and two distinct chromosomal instability gene expression signatures in order to address whether younger age at diagnosis is associated with increased tumour genome instability. We find that CIN, assessed by the two independently derived CIN expression signatures, is significantly associated with increased tumour size, ER negative or HER2 positive disease, higher tumour grade and younger age at diagnosis in ER negative breast cancer. These data support the hypothesis that chromosomal instability may be a defining feature of breast cancer biology and clinical outcome.
authors.affiliation: Cancer Research UK London Research Institute, London, WC2A 3LY, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Endesfelder
authors.forename: Nicholas
authors.initials: N
authors.lastname: McGranahan
authors.forename: Nicolai J
authors.initials: NJ
authors.lastname: Birkbak
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Szallasi
authors.forename: Maik
authors.initials: M
authors.lastname: Kschischo
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Graham
authors.forename: Charles
authors.initials: C
authors.lastname: Swanton
mesh_terms: D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry / Q000175:diagnosis / Q000235:genetics*; D043171:Chromosomal Instability; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D020411:Oligonucleotide Array Sequence Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D016896:Treatment Outcome
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human