title: Mammostrat as an immunohistochemical multigene assay for prediction of early relapse risk in the tamoxifen versus exemestane adjuvant multicenter trial pathology study.
abstract: OBJECTIVE
  Some postmenopausal patients with hormone-sensitive early breast cancer remain at high risk of relapse despite endocrine therapy and, in addition, might benefit from adjuvant chemotherapy. The challenge is to prospectively identify such patients. The Mammostrat test uses five immunohistochemical markers to stratify patients regarding recurrence risk and may inform treatment decisions. We tested the efficacy of this panel in the Tamoxifen versus Exemestane Adjuvant Multicenter (TEAM) trial.
  
  
  METHODS
  Pathology blocks from 4,598 TEAM patients were collected, and tissue microarrays (TMAs) were constructed. The cohort was 47% node-positive, and 36% of patients in the cohort were treated with adjuvant chemotherapy. Triplicate 0.6-mm(2) TMA cores were stained, and positivity for p53, HTF9C, CEACAM5, NDRG1, and SLC7A5 was assessed. Cases were assigned a Mammostrat risk score, and distant relapse-free survival (DRFS) and disease-free survival (DFS) were analyzed.
  
  
  RESULTS
  In multivariate regression analyses, which were corrected for conventional clinicopathologic markers, Mammostrat provided significant additional information on DRFS after endocrine therapy in estrogen receptor (ER) -positive node-negative patients (n = 1,226) who did not receive chemotherapy (P = .004). Additional analyses in all patients not exposed to chemotherapy, irrespective of nodal status (n = 2,559) and in the entire cohort (n = 3,837) showed Mammostrat scores provided additional information on DRFS in these groups (P = .001 and P < .001, respectively; multivariate analyses). No differences were seen between the two endocrine treatment regimens.
  
  
  CONCLUSIONS
  The Mammostrat score predicts DRFS for patients treated with exemestane and patients treated with tamoxifen followed by exemestane irrespective of nodal status and chemotherapy. The ability of this test to provide additional outcome data after treatment provides additional evidence of its use in risk stratification of ER-positive postmenopausal patients with breast cancer.
authors.affiliation: Ontario Institute for Cancer Research, Toronto, Ontario, Canada. john.bartlett@oicr.on.ca
authors.forename: John M S
authors.initials: JM
authors.lastname: Bartlett
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Bloom
authors.forename: Tammy
authors.initials: T
authors.lastname: Piper
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lawton
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Ross
authors.forename: Brian Z
authors.initials: BZ
authors.lastname: Ring
authors.forename: Robert S
authors.initials: RS
authors.lastname: Seitz
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Beck
authors.forename: Annette
authors.initials: A
authors.lastname: Hasenburg
authors.forename: Dirk
authors.initials: D
authors.lastname: Kieback
authors.forename: Hein
authors.initials: H
authors.lastname: Putter
authors.forename: Christos
authors.initials: C
authors.lastname: Markopoulos
authors.forename: Luc
authors.initials: L
authors.lastname: Dirix
authors.forename: Caroline
authors.initials: C
authors.lastname: Seynaeve
authors.forename: Daniel
authors.initials: D
authors.lastname: Rea
mesh_terms: D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; C056516:exemestane