title: Clinical relevance of the reappraisal of negative hormone receptor expression in breast cancer.
abstract: BACKGROUND
  Accurate assessment of estrogen (ER) and progesterone (PR) receptors is critical in predicting the response to endocrine therapies in breast cancer.
  
  
  METHODS
  From a series of 360 patients with breast invasive carcinoma assessed for hormone receptors by immunohistochemistry (IHC) in the 90's, we re-analysed, on the same tumour material, the cases considered negative (n = 164), i.e., ER-/PR- (n = 95), ER+/PR- (n = 63) and ER-/PR+ (n=6), and 16 of 196 ER+/PR+ tumours with unfavourable outcome. Concordance between the previous IHC (Streptavidin-Biotin-Peroxidase) method and the current one (Peroxidase-Indirect-Polymer) was determined by the McNemar's test. Relapse-free (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method.
  
  
  RESULTS
  From 101 ER- and 158 PR- cases, 38 (37.6%) and 58 (36.7%) became positive, increasing ER and PR expression from 71.9% and 56.1% to 82.5% and 72.2%, respectively (P<0.001). All 16 ER+/PR+ cases maintained their co-positivity, while all ER-/PR+ tumours changed to ER positive. Kaplan-Meier survival curves showed significant differences related to RFS and OS for PR, either in the whole series or in the subset (n = 151) submitted to hormonal treatment. The patients' subgroup with ER+/PR- tumours exhibited the worst prognosis.
  
  
  CONCLUSIONS
  The current IHC method improves the clinical usefulness of ER/PR assessment by decreasing the rate of false negative results.
authors.affiliation: Departamento de Matemática do Instituto Superior Técnico da Universidade Técnica de Lisboa, Lisboa, Portugal.
authors.forename: António E
authors.initials: AE
authors.lastname: Pinto
authors.forename: Filipa
authors.initials: F
authors.lastname: Areia
authors.forename: Teresa
authors.initials: T
authors.lastname: Pereira
authors.forename: Paula
authors.initials: P
authors.lastname: Cardoso
authors.forename: Mariana
authors.initials: M
authors.lastname: Aparício
authors.forename: Giovani L
authors.initials: GL
authors.lastname: Silva
authors.forename: Mónica C
authors.initials: MC
authors.lastname: Ferreira
authors.forename: Saudade
authors.initials: S
authors.lastname: André
keywords: Breast cancer; Estrogen receptors; Immunohistochemistry; Progesterone receptors; Prognosis