title: Cyclin E confers a prognostic value in premenopausal breast cancer patients with tumours exhibiting an infiltrative growth pattern.
abstract: OBJECTIVE
  To investigate the prognostic value of cyclin E in relation to tumour growth pattern by analysing stage II primary breast cancers from premenopausal women not subjected to any further adjuvant treatment. To analyse the value of cyclin E as a predictor of tamoxifen response, by comparing untreated and treated patients with oestrogen receptor positive tumours.
  
  
  METHODS
  Breast cancer samples, assembled in tissue microarrays, were immunohistochemically stained for cyclin E and evaluated regarding the presence of nuclear staining. The overall growth characteristics of each tumour were assessed using whole tissue sections.
  
  
  RESULTS
  Tumours displaying a pushing margin phenotype were strongly associated with high cyclin E levels, lymph node negative disease, a high histological grade and oestrogen receptor negativity, and exhibited a better prognosis compared to tumours with an infiltrative growth pattern. In the total cohort of non-treated patients (n = 187), cyclin E was not associated with recurrence free survival (RFS). However, when analysing the subgroup of tumours lacking a pushing growth pattern (n = 141), cyclin E was significantly associated with RFS, independent of histological grade and node status. There was no significant difference in tamoxifen response with regard to different cyclin E levels.
  
  
  CONCLUSIONS
  The prognostic value of cyclin E in premenopausal breast cancer is limited to patients with breast carcinomas exhibiting an exclusively infiltrative growth pattern. This limitation could be explained by the presence of a small but distinct subgroup of cyclin E-high breast cancers with a pushing margin phenotype and a more favourable outcome.
authors.affiliation: Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Berglund
authors.forename: M
authors.initials: M
authors.lastname: Stighall
authors.forename: K
authors.initials: K
authors.lastname: Jirström
authors.forename: L
authors.initials: L
authors.lastname: Rydén
authors.forename: M
authors.initials: M
authors.lastname: Fernö
authors.forename: B
authors.initials: B
authors.lastname: Nordenskjöld
authors.forename: G
authors.initials: G
authors.lastname: Landberg
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D019927:Cyclin E / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D017697:Premenopause; D011379:Prognosis; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D019927:Cyclin E; D009363:Neoplasm Proteins; D013629:Tamoxifen