Statement: Patients with undetermined  human epidermal growth factor receptor 2 expression cannot be accepted by either the primary trial or the secondary trial.
Primary_evidence: Inclusion Criteria:   Invasive breast cancer verified in a histological biopsy   Age 65 or younger   Estrogen receptor (ER), PgR and HER2 expression have been determined   No distant metastases present (M0)   The patient provides a written informed consent for study participation   The estimated risk of breast cancer recurrence is high (25% or higher within the first 5 years from the date of the diagnosis, over >35% within the first 10 years from the diagnosis) Exclusion Criteria:   Patients with breast cancer with "a special histological type" (mucinous, papillary, medullary, or tubular type of breast cancer) when no metastases are present in the ipsilateral axillary lymph nodes   The WHO performance status is moderate/poor, Z >1   The peripheral blood leukocyte count is less than 3.0 x 109/L, the blood granulocyte count is less than 1.5 x 109/L, or the blood thrombocyte count is less than 120 x 109/L   Any physical or mental disorder that is considered to prohibit administration of chemotherapy   Cardiac failure; severe cardiac arrythmia requiring regular medication
Secondary_evidence: Inclusion Criteria:   Females  18 years of age   Histologically confirmed invasive breast cancer   Planning for surgical resection of breast tumor and sentinel node or axillary lymph node resection   Planning neoadjuvant chemotherapy   HER2 positive disease   Measurable disease in the breast after diagnostic biopsy, defined as longest diameter  2.0 cm   Known estrogen receptor (ER) and progesterone receptor (PR) hormone receptor status at study entry   Normal bone marrow function   Normal hepatic function   Normal renal function   Subjects must sign an Institutional Review Board/Ethics Committee (IRB/EC)-approved informed consent form before any study specific procedures   Inclusion Criteria for Randomization:   Left ventricular ejection fraction (LVEF) of 55% by 2D echocardiogram   Complete all 4 cycles of run-in chemotherapy Exclusion Criteria:   Bilateral breast cancer   Presence of known metastases   Received prior treatment, including chemotherapy, biologic therapy, radiation or surgery with the exception of diagnostic biopsy for primary breast cancer   Other concomitant active malignancy or history of malignancy in the past 5 years except treated basal cell carcinoma of the skin or carcinoma in situ of the cervix   Pre-existing clinically significant ( grade 2) peripheral neuropathy   Any history of documented or current congestive heart failure, current high-risk uncontrolled arrhythmias, current angina pectoris requiring a medicinal product, current clinically significant valvular disease, current evidence of transmural infarction on electrocardiogram (ECG), or current poorly controlled hypertension   Severe dyspnea at rest requiring supplementary oxygen therapy   History of positivity for hepatitis B surface antigen, hepatitis C virus, or human immunodeficiency virus (HIV)   Recent infection requiring a course of systemic anti-infectives that were completed  14 days before enrollment (with the exception of uncomplicated urinary tract infection)   Woman of childbearing potential who is pregnant or is breast feeding   Woman of childbearing potential who is not consenting to use highly effective methods of birth control (eg, true abstinence [periodic abstinence (eg calendar ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception], sterilization, or other non-hormonal forms of contraception) during treatment and for at least 7 months after the last administration of the protocol specified treatment   Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study   Other investigational procedures while participating in this study are excluded   Subject has known sensitivity to any of the products to be administered during the study, including mammalian cell derived drug products, trastuzumab, murine proteins, or to any of the excipients   Subject previously has enrolled and/or has been randomized in this study   Subject likely to not be available to complete all protocol required study visits or procedures   History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the Investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion