title: A prospective, multicenter validation study of a prognostic index composed of S-phase fraction, progesterone receptor status, and tumour size predicts survival in node-negative breast cancer patients: NNBC, the node-negative breast cancer trial.
abstract: BACKGROUND
  In a retrospective study on node-negative breast cancer, a prognostic index consisting of a proliferation factor, S-phase fraction (SPF), progesterone receptor status (PR), and tumour size identified one-third of patients as high risk, with a sixfold increased risk of breast cancer death. This prospective multicenter cohort study was set up to validate the index.
  
  
  METHODS
  In 576 T1-2N0 patients <60 years, prospective analyses of PR and SPF were carried out. High risk was defined as ≥2 of the following: size >20 mm, PR-negativity, and high SPF (in the absence of SPF, Bloom-Richardson grade 3). Median follow-up was 17.8 years.
  
  
  RESULTS
  Thirty-one percent were high risk. In univariate analysis, the index was prognostic for breast cancer-specific survival after 5 years [hazard ratio (HR) = 4.7, 95% confidence interval (95% CI) 2.5-8.9], 10 years (HR = 2.2, 95% CI 1.5-3.3), and 15 years (HR = 1.7, 95% CI 1.2-2.5), and remained significant after adjustment for adjuvant medical treatment and age. In the 37% of patients with no risk factors, only one patient died of breast cancer the first 5 years.
  
  
  CONCLUSIONS
  This prospective study validates a prognostic index consisting of a proliferation factor, PR-status, and tumour size. The index may be helpful for prognostic considerations and for selection of patients in need of adjuvant therapy.
authors.affiliation: Department of Clinical Sciences, Division of Oncology, Lund University, Lund, Sweden. marie.klintman@med.lu.se
authors.forename: M
authors.initials: M
authors.lastname: Klintman
authors.forename: F
authors.initials: F
authors.lastname: Nilsson
authors.forename: P-O
authors.initials: PO
authors.lastname: Bendahl
authors.forename: M
authors.initials: M
authors.lastname: Fernö
authors.forename: G
authors.initials: G
authors.lastname: Liljegren
authors.forename: S
authors.initials: S
authors.lastname: Emdin
authors.forename: P
authors.initials: P
authors.lastname: Malmström
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000601:surgery; D049109:Cell Proliferation; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D008940:Mitotic Index; D011446:Prospective Studies; D011980:Receptors, Progesterone / Q000378:metabolism*; D016196:S Phase / Q000502:physiology*; D013534:Survival
chemical_list: D014408:Biomarkers, Tumor; D011980:Receptors, Progesterone
keywords: S-phase; breast cancer; prognosis; proliferation; prospective; validation