title: Prognostic molecular markers in women aged 35 years or younger with breast cancer: is there a difference from the older patients?
abstract: BACKGROUND
  Women aged ≤ 35 years with breast cancer have a poor prognosis, but their prognostic factors have not been clearly defined.
  
  
  OBJECTIVE
  To evaluate whether the molecular markers used in age-unspecified breast cancer could also be applied to women ≤ 35 years.
  
  
  METHODS
  Archival tumours from patients aged ≤ 35 years with stage I-III breast cancer were collected. Oestrogen receptor (ER), progesterone receptor (PR), HER2, Ki67 and P53 protein expression profiles in paraffin-embedded tissue sections were determined by immunohistochemistry. Tumours with an HER2 score of 2+ were further evaluated by fluorescence in situ hybridisation. Mutational analysis of exons 4-9 of the TP53 gene and exons 9 and 20 of the PIK3CA gene was carried out using direct sequencing analysis.
  
  
  RESULTS
  116 patients with a median follow-up duration of 62.7 months were included. In addition to tumour size and axillary lymph node status, univariate analysis showed that high Ki67 expression, ER-negative, HER2 overexpression, and TP53 mutations were associated with shorter overall survival. Multivariate analysis showed that high Ki67 expression (HR=3.93, p=0.005), HER2 overexpression (HR=3.21, p=0.013) and TP53 mutations (HR=4.44, p=0.005) were associated with shorter overall survival. PR expression and PIK3CA mutations were not associated with survival.
  
  
  CONCLUSIONS
  For women ≤ 35 years, TP53 mutations, Ki67 and HER2 expressions are strong prognostic factors. The limited prognostic value of hormone receptors suggests that the prognostic markers used in age-unspecified breast cancer may not be completely fit for this population.
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ching-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: Yen-Shen
authors.initials: YS
authors.lastname: Lu
authors.forename: Chiun-Sheng
authors.initials: CS
authors.lastname: Huang
authors.forename: Kuan-Ting
authors.initials: KT
authors.lastname: Kuo
authors.forename: Chung-Chieh
authors.initials: CC
authors.lastname: Wang
authors.forename: San-Lin
authors.initials: SL
authors.lastname: You
authors.forename: Po-Han
authors.initials: PH
authors.lastname: Lin
authors.forename: Dwan-Ying
authors.initials: DY
authors.lastname: Chang
authors.forename: Wen-Hung
authors.initials: WH
authors.lastname: Kuo
authors.forename: King-Jen
authors.initials: KJ
authors.lastname: Chang
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000367:Age Factors; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D016158:Genes, p53; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000378:metabolism; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D013624:Taiwan / Q000453:epidemiology
chemical_list: D014408:Biomarkers, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D004273:DNA, Neoplasm; D005819:Genetic Markers; D019394:Ki-67 Antigen; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C484760:PIK3CA protein, human; C508053:ERBB2 protein, human