title: Factors predicting late recurrence for estrogen receptor-positive breast cancer.
abstract: BACKGROUND
  Adjuvant endocrine therapy beyond 5 years reduces recurrence in patients with estrogen receptor-positive breast cancer. We have previously shown that immunohistochemical markers (IHC4) and two gene expression profile tests (recurrence score [RS] and PAM50 risk of recurrence [ROR]) are associated with time to distant recurrence, and we have now assessed the value of each of these scores and routine clinical variables for predicting outcome, specifically in years 5 to 10.
  
  
  METHODS
  We used univariate and multivariable proportional hazards models to determine the prognostic value of all variables and scores (IHC4, RS, ROR) for distant recurrence, separately in years 0 to 5 and specifically for years 5 to 10 for all patients. All statistical tests were two-sided.
  
  
  RESULTS
  Nodal status and tumor size were at least as strong in years 5 to 10 as in years 0 to 5 (nodal status, years 5-10: χ² = 21.72 vs years 0-5: χ² = 11.08, both P < .001; tumor size, years 5-10: χ² = 10.52 vs years 0-5: χ² = 10.82, both P = .001). Ki67 and the overall IHC4 score were the only statistically significant biomarkers related to distant recurrence univariablely in the 5 to 10 year period (χ² = 8.67, χ² = 13.22, respectively). The ROR score was the strongest molecular prognostic factor in the late follow-up period (χ² = 16.29; P < .001), whereas IHC4 (χ² = 7.41) and RS (χ² = 5.55) were only weakly prognostic in this period. Similar results were seen for all subgroups and for all recurrences.
  
  
  CONCLUSIONS
  None of the IHC4 markers provided statistically significant prognostic information in years 5 to 10, except for nodal status and tumor size. ROR gave the strongest prognostic information in years 5 to 10. These results may help select patients who could benefit most from hormonal therapy beyond 5 years of treatment.
authors.affiliation: Affiliations of authors: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University, London, UK (IS, JC); Academic Department of Biochemistry, Royal Marsden Hospital, London, UK (MD, LZ, EL-K); NanoString Technologies, Seattle, WA (SF, JWC).
authors.forename: Ivana
authors.initials: I
authors.lastname: Sestak
authors.forename: Mitch
authors.initials: M
authors.lastname: Dowsett
authors.forename: Lila
authors.initials: L
authors.lastname: Zabaglo
authors.forename: Elena
authors.initials: E
authors.lastname: Lopez-Knowles
authors.forename: Sean
authors.initials: S
authors.lastname: Ferree
authors.forename: J Wayne
authors.initials: JW
authors.lastname: Cowens
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology*; D004334:Drug Administration Schedule; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000737:chemistry / Q000175:diagnosis*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000032:analysis*; D013997:Time Factors
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen
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