title: MammaPrint Pre-screen Algorithm (MPA) reduces chemotherapy in patients with early-stage breast cancer.
abstract: BACKGROUND
  Clinical and pathological parameters may overestimate the need for chemotherapy in patients with early-stage breast cancer. More accurate determination of the risk of distant recurrence is now possible with use of genetic tests, such as the 70-gene MammaPrint profile.
  
  
  OBJECTIVE
  A health technology assessment performed by a medical insurer in 2009 introduced a set of test eligibility criteria - the MammaPrint Pre-screen Algorithm (MPA) - applied in this study to determine the clinical usefulness of a pathology-supported genetic testing strategy, aimed at the reduction of healthcare costs.Methods. An implementation study was designed to take advantage of the fact that the 70-gene profile excludes analysis of hormone receptor and human epidermal growth factor receptor 2 (HER2) status, which form part of the MPA based partly on immunohistochemistry routinely performed in all breast cancer patients. The study population consisted of 104 South African women with early-stage breast carcinoma referred for MammaPrint. For the MammaPrint test, RNA was extracted from 60 fresh tumours (in 58 patients) and 46 formalin-fixed, paraffin-embedded (FFPE) tissue samples.
  
  
  RESULTS
  When applying the MPA for selection of patients eligible for MammaPrint testing, 95 of the 104 patients qualified. In this subgroup 62% (59/95) were classified as low risk. Similar distribution patterns for risk classification were obtained for RNA extracted from fresh tumours v. FFPE tissue samples.
  
  
  CONCLUSIONS
  The 70-gene profile classifies approximately 40% of early-stage breast cancer patients as low-risk compared with 15% using conventional criteria. In comparison, more than 60% were shown to be low risk with use of the MPA validated in this study as an appropriate strategy to prevent chemotherapy overtreatment in patients with early-stage breast cancer.
authors.affiliation: Department of Biomedical Sciences, Cape Peninsula University of Technology, Cape Town, South Africa. grantk@cput.ac.za
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Grant
authors.forename: Justus P
authors.initials: JP
authors.lastname: Apffelstaedt
authors.forename: Colleen A
authors.initials: CA
authors.lastname: Wright
authors.forename: Ettienne
authors.initials: E
authors.lastname: Myburgh
authors.forename: Rika
authors.initials: R
authors.lastname: Pienaar
authors.forename: Manie
authors.initials: M
authors.lastname: De Klerk
authors.forename: Maritha J
authors.initials: MJ
authors.lastname: Kotze
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D013019:South Africa; D059467:Transcriptome
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human