title: Predicting anthracycline benefit: have we made any progress?
abstract: OBJECTIVE
  The benefit from anthracycline-based vs. nonanthracycline-based adjuvant therapy is not experienced by all breast cancer patients. Identification of the individuals to derive this benefit may be guided by predictive biomarkers. This review focuses on the search for biomarkers, particularly focusing on the potential roles for HER-2 and/or topoisomerase IIalpha.
  
  
  RESULTS
  Clarification of differential sensitivity to anthracyclines is complicated due to disease heterogeneity, complexity of underlying biological pathways, biomarker detection methods and features of study design. Meta-analyses suggest anthracycline benefit is restricted to patients with HER-2 amplified disease. However, diversity within HER-2 positive and HER-2 negative subgroups limits the use of HER-2 status as an independent marker. Certainly, subgroups within HER-2 negative disease have demonstrable incremental benefit from anthracycline-based therapy. Regarding topoisomerase IIalpha, the best method of detection and predictive role remain unclear.
  
  
  CONCLUSIONS
  Although progress has been made in defining breast cancer subgroups and identifying patients with general chemosensitivity, we do not yet have reliable predictive markers for anthracyclines. With current evidence, neither HER-2 status nor topoisomerase IIalpha status can be considered clinically valuable in guiding prescription of anthracyclines. Disease heterogeneity may dictate prediction by tumour profiles, rather than any single marker. These profiles may incorporate a panel of markers, including not only tumour features, such as HER-2 and topoisomerase IIalpha, but also host-determined features, such as stroma and stroma-anthracycline interaction. A new generation of well powered clinical trials that attempt to incorporate breast cancer heterogeneity may bridge the gap between available results and individual patient care.
authors.affiliation: Sandro Pitigliani Medical Oncology Unit, Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Prato, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Moretti
authors.forename: Catherine
authors.initials: C
authors.lastname: Oakman
authors.forename: Angelo
authors.initials: A
authors.lastname: Di Leo
mesh_terms: D018943:Anthracyclines / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases