title: Human epidermal growth receptor-2 overexpressing early operable primary breast cancers in older (≥70 years) women: biology and clinical outcome in comparison with younger (<70 years) patients.
abstract: BACKGROUND
  There is dearth of literature reporting the prevalence and biological characteristics as well as the long-term clinical outcome of human epidermal growth factor receptor-2 (HER2) overexpressing tumours in older women. Currently, research involving trastuzumab at large focuses on the younger population. This study aimed to analyse their biological characteristics and to compare them with their younger counterparts from a single centre with a long-term clinical follow-up.
  
  
  METHODS
  Over 37 years (1973-2010), 1758 older (≥70 years) women with early operable (<5 cm) primary breast cancer were managed in a dedicated clinic and have complete clinical information available. Of these, 813 patients underwent primary surgery and 575 had good quality tumour samples available for tissue microarray analysis using indirect immunohistochemistry. Comparison was made with data from a well-characterised younger (<70 years) series (N = 1711) treated between 1986 and 1998 (before adjuvant trastuzumab became standard) in our institution. Forty five (7.6%) and 140 (8.2%) patients from the older and younger series, respectively, had HER2-positive tumours.
  
  
  RESULTS
  HER2 overexpression was seen in 45 (7.6%) older women and 140 (8.2%) in younger patients (P = 0.56). HER2 overexpressing tumours in older women when compared with that in their younger counterparts were associated with low Ki67 and high bcl2 expression (P < 0.05). Only 26% of the younger patients and none of the older patients received adjuvant chemotherapy, and no patients at the time received trastuzumab. However, there was no significant difference in the outcome of the two age groups (5-year breast cancer-specific survival rate: <70 years = 65% versus >70 years = 70%, P = 0.51).
  
  
  CONCLUSIONS
  HER2 overexpressing tumours in older women showed relatively a less aggressive phenotype and did not show any inferior long-term clinical outcome despite not having received chemotherapy when compared with the younger patients. The precise role of different adjuvant systemic therapies in this population needs to be delineated.
authors.affiliation: School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: B M
authors.initials: BM
authors.lastname: Syed
authors.affiliation: School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Green
authors.affiliation: School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: I O
authors.initials: IO
authors.lastname: Ellis
authors.affiliation: School of Medicine, University of Nottingham, Nottingham, UK. Electronic address: kl.cheung@nottingham.ac.uk.
authors.forename: K L
authors.initials: KL
authors.lastname: Cheung
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D015996:Survival Rate; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: HER2 overexpressing; breast cancer; older women