title: Immunological subtypes in breast cancer are prognostic for invasive ductal but not for invasive lobular breast carcinoma.
abstract: BACKGROUND
  Classical patient and tumour characteristics are the benchmark of personalised breast cancer (BC) management. Recent evidence has demonstrated that immune and molecular profiling of BC may also play an important role. Despite evidence of differences between invasive ductal (IDC) and lobular (ILC) BC, they are infrequently accounted for when making treatment decisions for individual patients. The purpose of this study was to investigate the relevance of the tumour immune response in the major histological subtypes of BC. We also assessed the relationship between immune responses and molecular subtypes and their prognostic potential.
  
  
  METHODS
  Immunostains were done for HLA-I, HLA-E, HLA-G, Tregs, NK cells and CTLs for the composition of the immune profiles and Ki67, EGFR, CK5/6, ER, PR and HER2 for molecular profiles in 714 breast cancer patients who underwent primary surgery.
  
  
  RESULTS
  No significant association was found between IDC (90.6%) and ILC (9.4%) and tumour immune subtypes (P=0.4) and molecular subtypes (P=0.4). However, for the relapse-free period (RFP) tumour immune subtyping was prognostic (P=0.002) in IDC, but not ILC. Contrary to ILC, IDC patients frequently expressed higher cleaved caspase-3 and Ki67, which was prognostic. Intermediate immune-susceptible IDC expressing high cleaved caspase-3 or Ki67 showed worse RFP than those with low expression (caspase-3: P=0.004; Ki67: P=0.002); this was not seen for ILC or in high or low immune-susceptible tumour types for either IDC or ILC.
  
  
  CONCLUSIONS
  Tumour immune characteristics and host immune responses are prognostic in IDC, but not ILC. In addition, tumour immune profiles are only prognostic in Luminal A tumours.
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: C C
authors.initials: CC
authors.lastname: Engels
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: D B Y
authors.initials: DB
authors.lastname: Fontein
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: P J K
authors.initials: PJ
authors.lastname: Kuppen
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: de Kruijf
authors.affiliation: Department of pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: V T H B M
authors.initials: VT
authors.lastname: Smit
authors.affiliation: Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J W R
authors.initials: JW
authors.lastname: Nortier
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: Liefers
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: C J H
authors.initials: CJ
authors.lastname: van de Velde
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Bastiaannet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000276:immunology* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000276:immunology* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult
chemical_list: D019394:Ki-67 Antigen; C505407:CASP3 protein, human; D053148:Caspase 3