title: Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20.
abstract: OBJECTIVE
  The 21-gene OncotypeDX recurrence score (RS) assay quantifies the risk of distant recurrence in tamoxifen-treated patients with node-negative, estrogen receptor (ER)-positive breast cancer. We investigated the association between RS and risk for locoregional recurrence (LRR) in patients with node-negative, ER-positive breast cancer from two National Surgical Adjuvant Breast and Bowel Project (NSABP) trials (NSABP B-14 and B-20).
  
  
  METHODS
  RS was available for 895 tamoxifen-treated patients (from both trials), 355 placebo-treated patients (from B-14), and 424 chemotherapy plus tamoxifen-treated patients (from B-20). The primary end point was time to first LRR. Distant metastases, second primary cancers, and deaths before LRR were censored.
  
  
  RESULTS
  In tamoxifen-treated patients, LRR was significantly associated with RS risk groups (P < .001). The 10-year Kaplan-Meier estimate of LRR was 4.% (95% CI, 2.3% to 6.3%) for patients with a low RS (< 18), 7.2% (95% CI, 3.4% to 11.0%) for those with intermediate RS (18-30), and 15.8% (95% CI, 10.4% to 21.2%) for those with a high RS (> 30). There were also significant associations between RS and LRR in placebo-treated patients from B-14 (P = .022) and in chemotherapy plus tamoxifen-treated patients from B-20 (P = .028). In multivariate analysis, RS was an independent significant predictor of LRR along with age and type of initial treatment.
  
  
  CONCLUSIONS
  Similar to the association between RS and risk for distant recurrence, a significant association exists between RS and risk for LRR. This information has biologic consequences and potential clinical implications relative to locoregional therapy decisions for patients with node-negative and ER-positive breast cancer.
authors.affiliation: National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers, Departmentof Biostatistics, Graduate School of Public Health, University of Pittsburgh, USA. tmamounas@aultman.com
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Mamounas
authors.forename: Gong
authors.initials: G
authors.lastname: Tang
authors.forename: Bernard
authors.initials: B
authors.lastname: Fisher
authors.forename: Soonmyung
authors.initials: S
authors.lastname: Paik
authors.forename: Steven
authors.initials: S
authors.lastname: Shak
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Costantino
authors.forename: Drew
authors.initials: D
authors.lastname: Watson
authors.forename: Charles E
authors.initials: CE
authors.lastname: Geyer
authors.forename: D Lawrence
authors.initials: DL
authors.lastname: Wickerham
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D002986:Clinical Trials as Topic; D020869:Gene Expression Profiling; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011960:Receptors, Estrogen / Q000378:metabolism*; D018570:Risk Assessment; D013629:Tamoxifen / Q000627:therapeutic use
chemical_list: D011960:Receptors, Estrogen; D013629:Tamoxifen