title: Translating neoadjuvant therapy into survival benefits: one size does not fit all.
abstract: Neoadjuvant therapy has been established as an effective therapeutic approach for patients with locally advanced breast cancer. Similar outcomes between neoadjuvant and adjuvant chemotherapy have been demonstrated in several trials. Nevertheless, neoadjuvant therapy has some advantages over adjuvant therapy, including tumour downstaging, in vivo assessment of therapeutic efficacy, reduced treatment durations, and the need to enrol fewer patients for clinical trials to reach their preplanned objectives. The number of neoadjuvant trials in patients with breast cancer has increased substantially in the past 5 years, particularly in the context of HER2-positive disease. Substantial improvements in the pathological complete response rate to anti-HER2 therapy, a proposed surrogate end point for long-term clinical benefit, have been observed with neoadjuvant dual-agent HER2 blockade. Thus, it was hypothesized that this approach would provide additional survival benefits over standard-of-care therapy with the anti-HER2 antibody trastuzumab in the adjuvant setting. Emerging data, however, are calling this notion into question. We discuss potential reasons why results of neoadjuvant trials of targeted therapies have not been mirrored in the adjuvant setting, and other than inherent differences in clinical-trial designs and statistical power, we consider how the biology of the disease, patient characteristics, and drug administration and schedule might influence the results.
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.|Medical Oncology Department, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Paseo Vall d'Hebron 119-129, 08035 Barcelona, Spain.|Faculty of Medicine, Universitat Autònoma de Barcelona (UAB), Campus de la UAB, Plaza Cívica, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: De Mattos-Arruda
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
authors.forename: Ronglai
authors.initials: R
authors.lastname: Shen
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
authors.affiliation: Medical Oncology Department, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Paseo Vall d'Hebron 119-129, 08035 Barcelona, Spain.|Ramon y Cajal University Hospital, Ctra. de Colmenar Viejo, 28034 Madrid, Spain.|Medica Scientia Innovation Research (MedSIR), C/ Rambla Catalunya 2, 2D, 08007 Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Cortés
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic / Q000379:methods; D019008:Drug Resistance, Neoplasm; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation / Q000235:genetics; D020360:Neoadjuvant Therapy; D018579:Patient Selection; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human