title: Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group.
abstract: Uncontrolled proliferation is a hallmark of cancer. In breast cancer, immunohistochemical assessment of the proportion of cells staining for the nuclear antigen Ki67 has become the most widely used method for comparing proliferation between tumor samples. Potential uses include prognosis, prediction of relative responsiveness or resistance to chemotherapy or endocrine therapy, estimation of residual risk in patients on standard therapy and as a dynamic biomarker of treatment efficacy in samples taken before, during, and after neoadjuvant therapy, particularly neoadjuvant endocrine therapy. Increasingly, Ki67 is measured in these scenarios for clinical research, including as a primary efficacy endpoint for clinical trials, and sometimes for clinical management. At present, the enormous variation in analytical practice markedly limits the value of Ki67 in each of these contexts. On March 12, 2010, an international panel of investigators with substantial expertise in the assessment of Ki67 and in the development of biomarker guidelines was convened in London by the co-chairs of the Breast International Group and North American Breast Cancer Group Biomarker Working Party to consider evidence for potential applications. Comprehensive recommendations on preanalytical and analytical assessment, and interpretation and scoring of Ki67 were formulated based on current evidence. These recommendations are geared toward achieving a harmonized methodology, create greater between-laboratory and between-study comparability, and allow earlier valid applications of this marker in clinical practice.
authors.affiliation: Department of Biochemistry, Royal Marsden Hospital and Breakthrough Breast Cancer Centre, Fulham Road, London, UK. mitch.dowsett@icr.ac.uk
authors.forename: Mitch
authors.initials: M
authors.lastname: Dowsett
authors.forename: Torsten O
authors.initials: TO
authors.lastname: Nielsen
authors.forename: Roger
authors.initials: R
authors.lastname: A'Hern
authors.forename: John
authors.initials: J
authors.lastname: Bartlett
authors.forename: R Charles
authors.initials: RC
authors.lastname: Coombes
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
authors.forename: Matthew
authors.initials: M
authors.lastname: Ellis
authors.forename: N Lynn
authors.initials: NL
authors.lastname: Henry
authors.forename: Judith C
authors.initials: JC
authors.lastname: Hugh
authors.forename: Tracy
authors.initials: T
authors.lastname: Lively
authors.forename: Lisa
authors.initials: L
authors.lastname: McShane
authors.forename: Soon
authors.initials: S
authors.lastname: Paik
authors.forename: Frederique
authors.initials: F
authors.lastname: Penault-Llorca
authors.forename: Ljudmila
authors.initials: L
authors.lastname: Prudkin
authors.forename: Meredith
authors.initials: M
authors.lastname: Regan
authors.forename: Janine
authors.initials: J
authors.lastname: Salter
authors.forename: Christos
authors.initials: C
authors.lastname: Sotiriou
authors.forename: Ian E
authors.initials: IE
authors.lastname: Smith
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.forename: Jo Anne
authors.initials: JA
authors.lastname: Zujewski
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hayes
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic / Q000379:methods; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D020360:Neoadjuvant Therapy / Q000379:methods; D011237:Predictive Value of Tests; D011379:Prognosis; D040081:Protein Array Analysis; D015203:Reproducibility of Results
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen