title: Research issues affecting preoperative systemic therapy for operable breast cancer.
abstract: Preoperative systemic therapy (PST) in operable breast cancer allows a small increase in breast conservation rates and has significant potential as a research platform. PST offers the ability to discern treatment effect in vivo, and may allow smaller trials targeting specific breast cancer subtypes and making more efficient use of resources. Early observations of a specific outcome of interest in individual patient subgroups may improve the design of larger definitive randomized adjuvant trials using survival as a main outcome. PST offers the potential for therapeutic adjustments midcourse, which assumes the existence of validated intermediate end points and effective alternative therapies. This article reviews critical research issues affecting the design of PST trials, including the appropriate selection of trial end points and markers for long-term outcome, baseline marker expression as a predictor of response, and statistical considerations using novel trial designs. Key issues regarding optimal tumor subtype selection for individual trials, novel approaches using nontherapeutic window trial designs, and ethical and advocacy considerations are also discussed. PST requires an experienced and cohesive multidisciplinary team for it to fulfill its potential in both research and clinical care.
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans St, Room 189, Baltimore, MD 21231-1000, USA. awolff@jhmi.edu
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Wolff
authors.forename: Donald
authors.initials: D
authors.lastname: Berry
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Carey
authors.forename: Marco
authors.initials: M
authors.lastname: Colleoni
authors.forename: Mitchell
authors.initials: M
authors.lastname: Dowsett
authors.forename: Matthew
authors.initials: M
authors.lastname: Ellis
authors.forename: Judy E
authors.initials: JE
authors.lastname: Garber
authors.forename: David
authors.initials: D
authors.lastname: Mankoff
authors.forename: Soonmyung
authors.initials: S
authors.lastname: Paik
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
authors.forename: Mary Lou
authors.initials: ML
authors.lastname: Smith
authors.forename: JoAnne
authors.initials: J
authors.lastname: Zujewski
mesh_terms: D020533:Angiogenesis Inhibitors / Q000600:supply & distribution / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D015415:Biomarkers; D035843:Biomedical Research; D001943:Breast Neoplasms / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy*; D049109:Cell Proliferation; D015340:Epidemiologic Research Design; D066246:ErbB Receptors; D026690:Ethics, Clinical; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015412:Mastectomy, Segmental; D020360:Neoadjuvant Therapy; D010344:Patient Advocacy; D011300:Preoperative Care; D011379:Prognosis; D011987:Receptors, Steroid; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D015415:Biomarkers; D011987:Receptors, Steroid; D066246:ErbB Receptors