title: Comparative effectiveness of neoadjuvant therapy for HER2-positive breast cancer: a network meta-analysis.
abstract: BACKGROUND
  The growing number of antihuman epidermal growth factor receptor-2 (HER2) agents suggests the need for defining the optimal choice of neoadjuvant therapy for HER2-positive breast cancer. This study aims to assess the efficacy and safety of neoadjuvant therapy for HER2-positive breast cancer.
  
  
  METHODS
  Randomized trials that compared different anti-HER2 regimens in the neoadjuvant setting were included. The odds ratio (OR) for pathological complete response (pCR), treatment completion, and safety was utilized for pooling effect sizes. Network meta-analysis using a Bayesian statistical model was performed to combine the direct and indirect evidence of neoadjuvant therapy for HER2-positive breast cancer. All statistical tests were two-sided.
  
  
  RESULTS
  A database search identified 1047 articles, with 10 studies meeting the eligibility criteria. A total of 2247 patients in seven different treatment arms were assessed. Anti-HER2 agents evaluated included trastuzumab (tzmb), lapatinib (lpnb), and pertuzumab (pzmb). Network meta-analysis showed no statistically significant difference between dual targeting treatment arms; however, lpnb reduced treatment completion due to adverse events. Patients in dual targeting arms had statistically significantly more pCR than those in other treatment arms (chemotherapy [CT] + tzmb + pzmb vs CT + tzmb, OR = 2.29, 95% credibility interval = 1.02 to 5.02, P = .02). The surface under the cumulative ranking probability curve indicated that CT + tzmb + pzmb had the highest probability of being the best treatment arm in terms of pCR.
  
  
  CONCLUSIONS
  This study indicates that combining two anti-HER2 agents with CT is the most effective treatment modality in the neoadjuvant setting for HER2-positive breast cancer.
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan (AN, TH, HJ, MT, TS, AM, TM, KO, YK); Department of Surgery and Cancer, Imperial College London, London, UK (HA, TA).
authors.forename: Aiko
authors.initials: A
authors.lastname: Nagayama
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan (AN, TH, HJ, MT, TS, AM, TM, KO, YK); Department of Surgery and Cancer, Imperial College London, London, UK (HA, TA). tetsu@z7.keio.jp okabayashikoji@gmail.com.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Hayashida
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan (AN, TH, HJ, MT, TS, AM, TM, KO, YK); Department of Surgery and Cancer, Imperial College London, London, UK (HA, TA).
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Jinno
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan (AN, TH, HJ, MT, TS, AM, TM, KO, YK); Department of Surgery and Cancer, Imperial College London, London, UK (HA, TA).
authors.forename: Maiko
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan (AN, TH, HJ, MT, TS, AM, TM, KO, YK); Department of Surgery and Cancer, Imperial College London, London, UK (HA, TA).
authors.forename: Tomoko
authors.initials: T
authors.lastname: Seki
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan (AN, TH, HJ, MT, TS, AM, TM, KO, YK); Department of Surgery and Cancer, Imperial College London, London, UK (HA, TA).
authors.forename: Akiko
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan (AN, TH, HJ, MT, TS, AM, TM, KO, YK); Department of Surgery and Cancer, Imperial College London, London, UK (HA, TA).
authors.forename: Takeshi
authors.initials: T
authors.lastname: Murata
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan (AN, TH, HJ, MT, TS, AM, TM, KO, YK); Department of Surgery and Cancer, Imperial College London, London, UK (HA, TA).
authors.forename: Hutan
authors.initials: H
authors.lastname: Ashrafian
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan (AN, TH, HJ, MT, TS, AM, TM, KO, YK); Department of Surgery and Cancer, Imperial College London, London, UK (HA, TA).
authors.forename: Thanos
authors.initials: T
authors.lastname: Athanasiou
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan (AN, TH, HJ, MT, TS, AM, TM, KO, YK); Department of Surgery and Cancer, Imperial College London, London, UK (HA, TA). tetsu@z7.keio.jp okabayashikoji@gmail.com.
authors.forename: Koji
authors.initials: K
authors.lastname: Okabayashi
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan (AN, TH, HJ, MT, TS, AM, TM, KO, YK); Department of Surgery and Cancer, Imperial College London, London, UK (HA, TA).
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001499:Bayes Theorem; D014408:Biomarkers, Tumor / Q000032:analysis / Q000037:antagonists & inhibitors*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy*; D057186:Comparative Effectiveness Research; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D016017:Odds Ratio; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000037:antagonists & inhibitors*; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000077341:Lapatinib; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C485206:pertuzumab