Inclusion Criteria:

• Subjects with operable, node-positive or high-risk node-negative (see #3 below) HER2-positive breast carcinoma are eligible for the study, provided they satisfy the following criteria.

  • 1. Subjects must demonstrate willingness to and be able to participate in the study and to adhere to dose and visit schedules
  • 2. Subjects must be of female gender and >= 18 years of age

  • 3. Subjects must have been diagnosed with operable, histologically confirmed adenocarcinoma of the breast with no clinical or radiological evidence of metastatic disease but with otherwise high or intermediate risk tumor characteristics:

    • node-positive: T1-3, N1-2, M0 OR

    • node-negative AND at least one of the following features:

      • Tumor >2 cm or

      • Tumor >1 cm and

        • Negative ER/PR or
        • Malignancy Grade 2-3 or
        • Presence of peritumoral vascular invasion or
        • Age <35 years
  • HER2-positive by FISH (with gene amplification) or 3+ using immunohistochemistry
  • Subjects must have had complete resection (R0) of the primary tumor and axillary lymph nodes (or must have negative sentinel node[s])
  • Baseline LVEF by MUGA scan or echocardiogram (ECHO) >=55%
  • ECOG-performance status of 0-1
  • Adequate postoperative bone marrow function with neutrophils >=1.5 x 10^9/l, platelets >=100 x 10^9/l and hemoglobin >=LLN
  • Adequate renal function: calculated creatinine clearance >=50 ml/min
  • Adequate postoperative liver function with a total bilirubin < ULN, alkaline phosphatase <2.5 times the ULN and AST <1.5 times the ULN
  • Subjects must be free of any clinically relevant disease that would, in the principal investigator's and/or sponsor's opinion, interfere with the conduct of the study or study evaluations
  • Subjects of childbearing potential (including women who are less than one year postmenopausal and will be sexually active during the study) must agree to use a medically accepted method of contraception, while receiving protocol-specified medication and for 30 days (or as per local requirements) after stopping the medication or be surgically sterilized prior to screening
  • Subjects must be able to provide written informed consent

Exclusion Criteria:

• Subject who meets any of the following exclusion criteria will be disqualified from participation in the study:

  • Clinical or radiological evidence of metastatic disease
  • Prior radiotherapy, chemotherapy or biotherapy for the currently diagnosed breast cancer prior to randomization
  • Clinically significant pericardial effusion

  • Serious cardiac illness including, but not confined to

    • history of documented congestive heart failure
    • history of any form of cardiomyopathy or active treatment for any form of cardiomyopathy
    • history of angina pectoris or documented transmural myocardial infarction, or active angina pectoris requiring medication
    • serious ventricular arrhythmias requiring medication or ICD therapy, uncontrolled supraventricular arrhythmias
    • clinically significant valvular disease
    • poorly controlled arterial hypertension (systolic BP >180 mmHg, diastolic BP >100 mmHg)
  • Sensory/motor neuropathy > grade 2 as defined by NCI-CTC
  • Pregnancy, or intending to become pregnant during the study
  • Nursing (breastfeeding) or intending to be nursing during the study

  • Any of the following clinical conditions:

    • Chronic obstructive pulmonary disease, requiring chronic treatment
    • Clinically significant active infections
    • A history of a psychological illness of condition, preventing the subject to understand the requirements of the study
    • Unstable regulation of diabetes mellitus
  • A situation or condition that, in the opinion of the investigator, may interfere with optimal participation in the study
  • Is on staff, affiliated with, or a family member of the staff personnel directly involved with this study
  • Usage of any investigational product within 30 days prior to enrollment
  • Participation in any other interventional clinical study involving drug, device or biological. This would not prohibit the patient from participating in a QOL, questionnaire, blood collection, or observational study.
  • Allergy to or sensitivity to the study drug or its excipients