title: St. Gallen endocrine response classes predict recurrence rates over time.
abstract: BACKGROUND
  In 2007 the St. Gallen consensus panel defined three endocrine response classes: highly endocrine responsive (ER-H), incomplete endocrine responsive (ER-I) and non-endocrine responsive tumours (ER-N). However, it is uncertain whether ER-I tumours are less responsive than ER-H tumours. We investigated whether recurrence rates vary over time between response classes. Additionally, we investigated the most predictive response class definition for tamoxifen benefit.
  
  
  METHODS
  We recollected tumours from 646 patients who participated in a randomized trial of adjuvant tamoxifen vs.
  
  
  METHODS
  Estrogen receptor (ER), progesterone receptor (PgR), HER2 status and tumour grade were revised centrally. St. Gallen classes were evaluated for recurrence free interval (RFI). Change in hazards over time was assessed. Subsequently, 6 alternative response class definitions were compared to optimize the cut-off for PgR and ER.
  
  
  RESULTS
  Schoenfeld residuals indicate a failure of proportional hazards between the endocrine response groups (p = 0.0001). The HR for recurrence risk shifted over time with the ER-H group initially being at lower risk (HR ER-H vs. ER-I 0.5), but after six years the recurrence risk increased (HR 1.9). The cut-off values for ER and PgR that statistically best discriminated RFI in the first 4 years for lymph node positive patients were ER ≥ 50% and PgR ≥ 75%.
  
  
  CONCLUSIONS
  We demonstrated a marked variability in endocrine therapy benefit. Patients with ER-H tumours have a larger benefit during adjuvant tamoxifen and in the first years after accomplishing of the therapy, but suffer from late recurrences. This might have implications for optimal treatment duration.
authors.affiliation: Department of Molecular Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Electronic address: r.koornstra@nki.nl.
authors.forename: R H T
authors.initials: RH
authors.lastname: Koornstra
authors.affiliation: Department of Molecular Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: K J
authors.initials: KJ
authors.lastname: Beelen
authors.affiliation: Department of Biometrics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: A D
authors.initials: AD
authors.lastname: Vincent
authors.affiliation: Department of Biometrics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: V
authors.initials: V
authors.lastname: van der Noort
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: van Diest
authors.affiliation: Department of Molecular Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: S C
authors.initials: SC
authors.lastname: Linn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000145:classification / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D012189:Retrospective Studies; D012307:Risk Factors; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; C508053:ERBB2 protein, human
keywords: Adjuvant therapy; Breast cancer; Endocrine responsiveness; Estrogen receptor; Progesterone receptor; Tamoxifen