title: Prediction of recurrence risk in early breast cancer using human epidermal growth factor 2 and cyclin A2.
abstract: BACKGROUND
  Human epidermal growth factor 2 (HER2) is one of the most important prediction factors, but only 25% - 30% of breast cancer patients HER2 are positive. It is unknown whether there are other molecular markers that could be used to predict prognosis and recurrence in HER2 negative patients. This study investigated correlations of cyclin A2 and HER2 levels with clinical outcomes in 281 patients with invasive breast cancer in order to identify whether cyclin A2 can serve as a prognostic factor in HER2 negative patients.
  
  
  METHODS
  Immunohistochemical staining was used to detect cyclin A2 and HER2 expression in 281 patients. Cyclin A2 and HER2 gene amplifications were analyzed using gene analysis and RT-PCR in 12 patients. Risk and survival estimates were analyzed using Log-rank, Kaplan-Meier, and Cox regression analysis; cyclin A2 and HER2 consistency with survival were analyzed using Kappa analysis.
  
  
  RESULTS
  Patients with higher cyclin A2 and HER2 expressions had significantly shorter disease-free survival periods (P = 0.047 and P = 0.05, respectively). Kappa analysis performed that cyclin A2 and HER2 showed a low Kappa index (kappa = 0.37), allowing us to conclude that cyclin A2 and HER2 detect different pathologies. Gene analysis and RT-PCR showed that cyclin A2 was upregulated in patients with early relapse; the average increase was 3.69 - 2.74 fold.
  
  
  CONCLUSIONS
  Cyclin A2 and HER2 are associated with proliferation and high recurrence, particularly when combined. Cyclin A2 is easily detected by nuclear staining and might be a useful biomarker for recurrence risk in HER2 negative patients.
authors.affiliation: Department of Medical Oncology, Peking University Third Hospital, Beijing 100191, China. huiping_l@ hotmail.com
authors.forename: Hui-ping
authors.initials: HP
authors.lastname: Li
authors.forename: Jia-fu
authors.initials: JF
authors.lastname: Ji
authors.forename: Kuan-yong
authors.initials: KY
authors.lastname: Hou
authors.forename: Yu-tao
authors.initials: YT
authors.lastname: Lei
authors.forename: Hong-mei
authors.initials: HM
authors.lastname: Zhao
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
authors.forename: Jian-ying
authors.initials: JY
authors.lastname: Liu
authors.forename: Mo-pei
authors.initials: MP
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Xiao
authors.forename: You-fan
authors.initials: YF
authors.lastname: Wang
authors.forename: You-yong
authors.initials: YY
authors.lastname: Lü
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D056751:Cyclin A2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D056751:Cyclin A2; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human