title: Centromere protein-A, an essential centromere protein, is a prognostic marker for relapse in estrogen receptor-positive breast cancer.
abstract: BACKGROUND
  Centromere protein A (CENP-A), an essential centromere protein, has been associated with high grade cancers. This study was undertaken to determine if CENP-A is a prognostic factor for breast cancer patients not receiving systemic therapy or predictive of response to tamoxifen or neoadjuvant chemotherapy.
  
  
  METHODS
  mRNA levels of CENP-A and CENP-B, a centromere protein that binds independently of CENP-A, were measured in breast cancer specimens from 484 patients receiving no systemic therapy, 276 patients receiving tamoxifen, and 233 patients treated with neoadjuvant chemotherapy. Associations between CENP-A, CENP-B, Ki-67, relapse, and chemotherapy response were determined.
  
  
  RESULTS
  CENP-A but not CENP-B was higher in estrogen receptor (ER)-negative tumors than ER-positive tumors and positively correlated with Ki-67 expression. Among patients with ER-positive disease who received no systemic therapy or tamoxifen, higher levels of CENP-A were associated with lower rates of 5-year distant relapse free survival (DRFS). On multivariate analyses including Ki-67, high CENP-A expression had a hazard ratio of 10.9 for relapse in patients with ER-positive disease not receiving systemic therapy (95% CI, 2.86 to 41.78; P = 0.00047) and 1.64 for patients with ER-positive disease receiving tamoxifen (95% CI, 0.99 to 2.71; P = 0.054). CENP-A was not an independent prognostic marker in ER-negative tumors. For both ER-positive and ER-negative tumors, CENP-A was not a significant independent predictor of chemotherapy response.
  
  
  CONCLUSIONS
  CENP-A was a significant independent prognostic marker for patients with ER-positive breast cancer not treated with systemic therapy but had limited predictive value in tamoxifen treated patients and was not predictive of response to neoadjuvant chemotherapy.
authors.affiliation: Department of Radiation Oncology, 1515 Holcombe Blvd,, University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA. slmcgove@mdanderson.org
authors.forename: Susan L
authors.initials: SL
authors.lastname: McGovern
authors.forename: Yuan
authors.initials: Y
authors.lastname: Qi
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
authors.forename: William F
authors.initials: WF
authors.lastname: Symmans
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchholz
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D000076247:Centromere Protein A; D051936:Centromere Protein B / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D013629:Tamoxifen / Q000627:therapeutic use
chemical_list: D018931:Antineoplastic Agents, Hormonal; D001324:Autoantigens; D014408:Biomarkers, Tumor; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D051936:Centromere Protein B; D002868:Chromosomal Proteins, Non-Histone; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013629:Tamoxifen