title: Two distinct local relapse subtypes in invasive breast cancer: effect on their prognostic impact.
abstract: OBJECTIVE
  Local relapse (LR) remains an important concern in breast cancer surveillance. Given the unique opportunity to study local recurrences in the breast in the absence of irradiation, we tested the possibility of identifying a particular tumor feature that might account for LR.
  
  
  METHODS
  Archival specimens from 235 patients belonging to the control arm (no radiotherapy) of the Milan 3 Trial were retrieved and included in this study. H&E-stained histologic slides were reviewed for diagnostic reassessment. A panel of biological variables was assessed by immunohistochemical/cytochemical staining.
  
  
  RESULTS
  Onset of LR was significantly linked only to patient's age, with a hazard ratio (HR) to relapse reduced by 60% in patients >50 years of age (P = 0.002). Univariate and multivariate Cox analyses in women <or=50 years of age indicated that only expression of hyaluronan in tumor cells was associated with LR risk (HR, 2.48; P = 0.0364 and HR, 2.34; P = 0.0580, respectively). In patients >50 years of age, lymph node and estrogen receptor status were significantly predictive of LR (HR, 3.34; P = 0.0113 and HR, 0.39; P = 0.0424, respectively). Multivariate analysis indicated that apart from lymph node positivity (HR, 3.48; P = 0.0120), none of the variables associated with LR in univariate analysis displayed an independent LR-predictive power. LR had a strong prognostic impact on distant metastasis in patients >50 years of age, whereas in younger women, LR did not affect the risk of metastasis.
  
  
  CONCLUSIONS
  These results support the notion that LR arises from two distinct mechanisms, one that is more frequent in young patients, associated with host characteristics, and is not linked with prognosis, and another that is less frequent, but is associated with tumor aggressiveness which represents a peculiar and distinct marker of breast tumor malignancy.
authors.affiliation: Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, University of Milan, Milan, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Casalini
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Carcangiu
authors.forename: Raija
authors.initials: R
authors.lastname: Tammi
authors.forename: Päivi
authors.initials: P
authors.lastname: Auvinen
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kosma
authors.forename: Pinuccia
authors.initials: P
authors.lastname: Valagussa
authors.forename: Marco
authors.initials: M
authors.lastname: Greco
authors.forename: Andrea
authors.initials: A
authors.lastname: Balsari
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ménard
authors.forename: Elda
authors.initials: E
authors.lastname: Tagliabue
mesh_terms: D000367:Age Factors; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis; D008207:Lymphatic Metastasis / Q000473:pathology; D008408:Mastectomy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D011960:Receptors, Estrogen / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D006820:Hyaluronic Acid