title: In patients younger than age 55 years with lymph node-negative breast cancer, proliferation by mitotic activity index is prognostically superior to adjuvant!
abstract: OBJECTIVE
  In breast cancer, different tools are used for prognostication and adjuvant systemic therapy selection. We compared the accuracy of the online program Adjuvant!, the Norwegian Breast Cancer Group (NBCG) guidelines, and the proliferation factor mitotic activity index (MAI) in patients with lymph node (LN) -negative disease (pN0).
  
  
  METHODS
  Adjuvant! and MAI thresholds were set to 90% to 95% breast cancer-specific survival (BCSS) rates. These thresholds were 95% for Adjuvant!, 3 for MAI, and as follows for NBCG: pT1 grade 1 + pT1a-b grade 2 to 3; all pN0M0 and estrogen receptor/progesterone receptor positive versus all others. In 516 patients younger than age 55 years (T1-3N0M0) without adjuvant systemic therapy, univariable and multivariable 10-year BCSS rates were estimated.
  
  
  RESULTS
  Median follow-up time was 118 months. The concordance between MAI and Adjuvant! or NBCG was fair (κ = 0.35 and κ = 0.29, respectively). Adjuvant!, NBCG, and MAI were all prognostically significant (P ≤ .001). In the univariable analysis, the 10-year BCSS of MAI less than 3 versus ≥ 3 was 95% v 71%, respectively, with a hazard ratio of 7.0. In multivariable analysis, MAI was superior to Adjuvant! and NBCG. The 10-year survival of Adjuvant! ≥ 95% versus less than 95% was 91% v 74%, respectively, but stratification by MAI identified subgroups with different prognosis. Similar results occurred for NBCG and MAI. Adjuvant! and NBCG were not prognostic to each other.
  
  
  CONCLUSIONS
  MAI is superior to Adjuvant! and NBCG in prognostication of patients with LN-negative breast cancer younger than age 55 years.
authors.affiliation: Stavanger University Hospital, Stavanger, Norway.
authors.forename: Tone Hoel
authors.initials: TH
authors.lastname: Lende
authors.forename: Emiel A M
authors.initials: EA
authors.lastname: Janssen
authors.forename: Einar
authors.initials: E
authors.lastname: Gudlaugsson
authors.forename: Feja
authors.initials: F
authors.lastname: Voorhorst
authors.forename: Rune
authors.initials: R
authors.lastname: Smaaland
authors.forename: Paul
authors.initials: P
authors.lastname: van Diest
authors.forename: Håvard
authors.initials: H
authors.lastname: Søiland
authors.forename: Jan P A
authors.initials: JP
authors.lastname: Baak
mesh_terms: D000328:Adult; D000367:Age Factors; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000175:diagnosis; D008875:Middle Aged; D008940:Mitotic Index; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D018579:Patient Selection; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor