Figure 1. Adjuvant trastuzumab study designs NCCTG N9831 1 year trastuzumab 4 x AC 12 x paclitaxel 90 mg/m2 HER2+ (IHC or FISH) NSABP B-31 HER2+ 1 year trastuzumab 4 x AC 4 x paclitaxel 175 mg/m2 2 (IHC or FISH) BCIRG 006 HER2+ 4 x AC 60/600 mg/m2 4 x docetaxel 100 mg/m2 6 x docetaxel and carboplatinum 75 mg/m2 AUC 6 1 year trastuzumab N=3222 1 year trastzumab AC→T AC→TH TCH (FISH) HERA 2 years trastuzumab HER2+ (IHC or FISH) Accepted CT: AC, EC, FAC, FEC, ET, AT, CMF 1 year trastuzumab Observation

Table 1. Overview of the trial populations in early breast cancer trastuzumab studies Stage I-IIIA, MO, invasive adenocarcinoma Trial NSABP B-31 NCCTG BCIRG 006 HERA N0(T1a T1b T1c)     N+  IHC  FISH  Randomized Prechemo Postchemo EF >50% >55% N0 node negative; N+ node positive;IHC immunohistochemistry; FISH fluorescent in situ hybridization; EF left ventricular ejection fraction required for study entry

Table 2. Efficacy in early breast cancer trastuzumab studies NSABP-B31 NCCTG N9831 combined analysis BCIRG 006 HERA ACTH TCH Regimen Follow-up Evaluable pts HR for DFS HR for DDFS HR for OS Concurrent 2 years 3351 Concurrent 2 years 3222 Sequential 1 year 3387 0.48 0.47 0.67 2p=3x10-12 2p=8x10-10 2p=0.015 0.49 NR 0.61 p<0.0001 p=0.0002 0.54 0.51 0.76 p<0.0001 p=0.26 TCH = docetaxel, carboplatinum, trastuzumab; TH = docetaxel, trastuzumab HR = hazard ratio; DFS = disease-free survival; DDFS = distant DFS; OS = overall survival

Table 3. Cardiac safety in early breast cancer trastuzumab studies NSABP-B31 NCCTG N9831 HERA BCIRG 006 AC P AC PH AC P AC PH ACP H Nil H 1 year AC T AC TH TCH CHF, n (%) Cardiac death, n 4 (0.8) 1 31 (4.1) 0 (0.3) 1 20 (3.5) 1 16 (2.5) 1 0 (0) 1 9 (0.5) 3 (0.3) 17 (1.7) 4 (0.4) NSABP (from JCO cardiotoxicity paper) and NCCTG (from SABCS 2005 poster) report cumulative rates, 006 reports raw rates H = Trastuzumab; P = paclitaxel; T = docetaxel; TCH = docetaxel, carboplatinum, trastuzumab; CHF = New York Heart Association Class 3-4 congestive heart failure