title: Twenty-one-gene recurrence score assay in BRCA-associated versus sporadic breast cancers: Differences based on germline mutation status.
abstract: BACKGROUND
  Biological differences between BRCA-associated breast cancer and sporadic breast cancer may warrant different adjuvant chemotherapy (ACRx) recommendations despite similar phenotypic features. A 21-gene expression profile (Oncotype DX) generates a prognostic recurrence score (RS) that predicts the ACRx benefit in patients with hormone receptor-positive breast cancer. No reports describe assay results for BRCA-associated breast cancer.
  
  
  METHODS
  A review of Memorial Sloan Kettering Cancer Center databases identified 4908 patients with hormone receptor-positive, node-negative breast cancer who underwent Oncotype DX testing between July 2006 and March 2014. BRCA1/BRCA2 carriers (cases) were identified and matched (1:2) by age at diagnosis and tumor size to noncarrier controls. Two-sample nonparametric tests were used to compare the baseline characteristics, RSs, and risk stratification between BRCA1 and BRCA2 patients. Conditional logistic regression was used to assess these differences by mutational status.
  
  
  RESULTS
  Fifty mutation-associated cases (19 BRCA1 cases and 31 BRCA2 cases) and 100 controls who were well matched for age (P = .9) and tumor size (P = .6) were included. BRCA1 and BRCA2 carriers had similar median RSs (P = .6) and risk category stratification (P = .3). The median RS was higher for cases versus controls (24 vs 16; P < .0001). Risk stratification also differed by mutational status (P = .0002). Cases had more high-risk disease (28% vs 7%) and intermediate-risk disease (56% vs 36%) and less low-risk disease (16% vs 57%). Cases were more likely than controls to receive ACRx (74% vs 46%; P = .002).
  
  
  CONCLUSIONS
  Germline BRCA-associated hormone receptor-positive breast cancer may be associated with intrinsically less favorable biology. Few affected carriers have RS indicating a clear absence of benefit from ACRx. The increased use of ACRx and benefit from ACRx in BRCA carriers may mitigate otherwise inferior outcomes.
authors: Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Payal D
authors: PD
authors: Shah
authors: Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Sujata
authors: S
authors: Patil
authors: Breast Medicine Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Maura N
authors: MN
authors: Dickler
authors: Clinical Genetics Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Kenneth
authors: K
authors: Offit
authors: Breast Medicine Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Clifford A
authors: CA
authors: Hudis
authors: Breast Medicine Service, Memorial Sloan Kettering Cancer Center, New York, New York.|Clinical Genetics Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Mark E
authors: ME
authors: Robson
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D015331:Cohort Studies; D016208:Databases, Factual; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D018095:Germ-Line Mutation; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D015996:Survival Rate; D014481:United States; D055815:Young Adult
keywords: BRCA; Oncotype DX; adjuvant chemotherapy; breast cancer; recurrence