title: A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients.
abstract: BACKGROUND
  The Oncotype DX assay was recently reported to predict risk for distant recurrence among a clinical trial population of tamoxifen-treated patients with lymph node-negative, estrogen receptor (ER)-positive breast cancer. To confirm and extend these findings, we evaluated the performance of this 21-gene assay among node-negative patients from a community hospital setting.
  
  
  METHODS
  A case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985 to 1994 and not treated with adjuvant chemotherapy. Cases (n = 220) were patients who died from breast cancer. Controls (n = 570) were breast cancer patients who were individually matched to cases with respect to age, race, adjuvant tamoxifen, medical facility and diagnosis year, and were alive at the date of death of their matched case. Using an RT-PCR assay, archived tumor tissues were analyzed for expression levels of 16 cancer-related and five reference genes, and a summary risk score (the Recurrence Score) was calculated for each patient. Conditional logistic regression methods were used to estimate the association between risk of breast cancer death and Recurrence Score.
  
  
  RESULTS
  After adjusting for tumor size and grade, the Recurrence Score was associated with risk of breast cancer death in ER-positive, tamoxifen-treated and -untreated patients (P = 0.003 and P = 0.03, respectively). At 10 years, the risks for breast cancer death in ER-positive, tamoxifen-treated patients were 2.8% (95% confidence interval [CI] 1.7-3.9%), 10.7% (95% CI 6.3-14.9%), and 15.5% (95% CI 7.6-22.8%) for those in the low, intermediate and high risk Recurrence Score groups, respectively. They were 6.2% (95% CI 4.5-7.9%), 17.8% (95% CI 11.8-23.3%), and 19.9% (95% CI 14.2-25.2%) for ER-positive patients not treated with tamoxifen. In both the tamoxifen-treated and -untreated groups, approximately 50% of patients had low risk Recurrence Score values.
  
  
  CONCLUSIONS
  In this large, population-based study of lymph node-negative patients not treated with chemotherapy, the Recurrence Score was strongly associated with risk of breast cancer death among ER-positive, tamoxifen-treated and -untreated patients.
authors.affiliation: Division of Research, Kaiser Permanente, Oakland, California, USA. laurel.habel@kp.org
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Habel
authors.forename: Steven
authors.initials: S
authors.lastname: Shak
authors.forename: Marlena K
authors.initials: MK
authors.lastname: Jacobs
authors.forename: Angela
authors.initials: A
authors.lastname: Capra
authors.forename: Claire
authors.initials: C
authors.lastname: Alexander
authors.forename: Mylan
authors.initials: M
authors.lastname: Pho
authors.forename: Joffre
authors.initials: J
authors.lastname: Baker
authors.forename: Michael
authors.initials: M
authors.lastname: Walker
authors.forename: Drew
authors.initials: D
authors.lastname: Watson
authors.forename: James
authors.initials: J
authors.lastname: Hackett
authors.forename: Noelle T
authors.initials: NT
authors.lastname: Blick
authors.forename: Deborah
authors.initials: D
authors.lastname: Greenberg
authors.forename: Louis
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: Bryan
authors.initials: B
authors.lastname: Langholz
authors.forename: Charles P
authors.initials: CP
authors.lastname: Quesenberry
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D011960:Receptors, Estrogen; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013629:Tamoxifen / Q000627:therapeutic use
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D013629:Tamoxifen