title: Intrinsic subtypes and genomic signatures of primary breast cancer and prognosis after systemic relapse.
abstract: Molecular subtypes and gene expression signatures are widely used in early breast cancer but their role in metastatic disease is less explored. Two hundred-twenty patients diagnosed with primary breast cancer and subsequent relapse in Stockholm, Sweden between 1997 and 2006 were identified and their primary tumor was assessed for immunohistochemistry (IHC)- and PAM50-based subtypes, risk of recurrence (ROR-S) score, 21-gene and 70-gene signatures using research-based microarray expression profiles. Clinical and pathological data were retrospectively collected. Post-relapse survival within intrinsic subtypes and genomic signatures was investigated by Kaplan-Meier and Cox regression methods. ROR weighted for proliferation index (ROR-P) was explored and the prognostic contribution provided when combined to a clinical model estimated as change in LR- χ(2). IHC classified 27%, 24%, 36% and 13% of the tumors as luminal A, luminal B, HER2+ and triple negative, respectively. PAM50 categorized 22%, 24%, 26%, 22%, 6% of the tumors as luminal A, luminal B, HER2-enriched, basal-like and normal-like. Triple negative and basal tumors had a significantly shorter median post-relapse survival in comparison with luminal. Overall, neither IHC nor PAM50 subtypes, 21- and 70- gene profiles were prognostic in multivariable models. Low and medium ROR-S had a longer survival compared with the high-risk group (23 vs 10 months; p = 0.04). ROR-P independently correlated with post-relapse survival (p = 0.002) and provided the most significant prognostic information when added to a clinical model. ROR score from primary tumor represents an independent prognostic factor of post-relapse survival beyond classical clinical and pathological variables.
authors.affiliation: Department of Oncology and Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden. Electronic address: claudette.falato@ki.se.
authors.forename: Claudette
authors.initials: C
authors.lastname: Falato
authors.affiliation: Department of Oncology and Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Tobin
authors.affiliation: Department of Oncology and Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden.
authors.forename: Julie
authors.initials: J
authors.lastname: Lorent
authors.affiliation: Department of Bioscience and Nutrition, Karolinska Institute and University Hospital, Stockholm, Sweden.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Lindström
authors.affiliation: Department of Oncology and Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
authors.affiliation: Department of Oncology and Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Foukakis
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy; D049109:Cell Proliferation; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D009363:Neoplasm Proteins
keywords: Gene expression signature; Intrinsic subtypes; Metastatic breast cancer; Proliferation score; Risk of recurrence score