title: Estrogen Receptor Expression in 21-Gene Recurrence Score Predicts Increased Late Recurrence for Estrogen-Positive/HER2-Negative Breast Cancer.
abstract: OBJECTIVE
  To identify the individual genes or gene modules that lead to the OncoptypeDx 21-gene recurrence score's reduced performance after 5 years and thereby identify indices of residual risk that may guide selection of patients for extended adjuvant therapy.
  
  
  METHODS
  We conducted a retrospective assessment of the relationship between (i) the individual genes and gene modules of the Recurrence Score and (ii) early (0-5 years) and late (5-10 years) recurrence rates in 1,125 postmenopausal patients with primary estrogen receptor-positive breast cancer treated with anastrozole or tamoxifen in the Arimidex, Tamoxifen, Alone or Combined (ATAC) randomized clinical trial.
  
  
  RESULTS
  In the HER2-negative population (n = 1,009), estimates of recurrence risk were similar between years 0-5 and 5-10 for proliferation and invasion modules but markedly different for the estrogen module and genes within it (all split at the median): for low estrogen module, annual recurrence rates were similar across the two time windows (2.06% vs. 2.46%, respectively); for high estrogen module, annual rates were 1.14% versus 2.72%, respectively (P interaction = 0.004). Estrogen receptor transcript levels showed inverse prediction across the time windows: HR, 0.88 (0.73-1.07) and 1.19 (0.99-1.43), respectively (P interaction = 0.03). Similar time-, module-, and estrogen-dependent relationships were seen for distant recurrence.
  
  
  CONCLUSIONS
  Patients with tumors with high estrogen receptor transcript levels benefit most from 5 years' endocrine therapy but show increased recurrence rates after 5 years and may benefit from extended therapy. Improved prognostic profiles may be created by considering period of treatment and follow-up time.
authors.affiliation: Royal Marsden Hospital and Breakthrough Breast Cancer Centre, Institute of Cancer Research, London, United Kingdom. mitch.dowsett@icr.ac.uk.
authors.forename: Mitch
authors.initials: M
authors.lastname: Dowsett
authors.affiliation: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Ivana
authors.initials: I
authors.lastname: Sestak
authors.affiliation: Royal Marsden Hospital and Breakthrough Breast Cancer Centre, Institute of Cancer Research, London, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Buus
authors.affiliation: Royal Marsden Hospital and Breakthrough Breast Cancer Centre, Institute of Cancer Research, London, United Kingdom.
authors.forename: Elena
authors.initials: E
authors.lastname: Lopez-Knowles
authors.affiliation: Department of Pathology, Western Infirmary, Glasgow, United Kingdom.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mallon
authors.affiliation: Christie Hospital, Manchester Breast Centre and Breakthrough Breast Cancer Research Unit, Manchester, United Kingdom.
authors.forename: Anthony
authors.initials: A
authors.lastname: Howell
authors.affiliation: Department of Surgical Oncology, University of Newcastle, Newcastle Mater Hospital, New South Wales, Australia.
authors.forename: John F
authors.initials: JF
authors.lastname: Forbes
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Aman
authors.initials: A
authors.lastname: Buzdar
authors.affiliation: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
mesh_terms: D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D009364:Neoplasm Recurrence, Local; D012333:RNA, Messenger / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen