Statement: Sufferers of Systemic lupus erythematosus are excluded from the primary trial but may still be eligible for the secondary trial.
Primary_evidence: DISEASE CHARACTERISTICS:   Histologically confirmed adenocarcinoma of the breast, meeting one of the following criteria:   Metastatic disease   High-risk disease, defined as early-stage disease with pathologic involvement of locoregional lymph nodes   Patients who are/will be receiving standard adjuvant trastuzumab [Herceptin®] for high-risk disease will participate in this study during the single-agent trastuzumab portion of their therapy   No clinical or radiographical evidence of active disease   Not eligible for therapy of known curative potential for metastatic breast cancer   HER2/neu-overexpressing disease, defined as HER2/neu positive by IHC 3+ staining or by FISH+ amplification   Stable CNS disease allowed provided it has been adequately treated and is not under active treatment   Hormone receptor status not specified   PATIENT CHARACTERISTICS:   Menopausal status not specified   ECOG performance status 0-1   ANC > 1,000/mm^3   Platelet count > 100,000/mm^3   Serum creatinine < 2.0 mg/dL   Serum bilirubin  2.0 mg/dL (unless elevation is due to known Gilbert's syndrome)   AST/ALT  2 times upper limit of normal (ULN)   Alkaline phosphatase  5 times ULN   Not pregnant or nursing   Negative pregnancy test   Fertile patients must use effective contraception   Cardiac ejection fraction normal by MUGA OR  45% by ECHO   No other malignancies within the past 5 years, except for carcinoma in situ of the cervix, superficial nonmelanoma skin cancer, or superficial bladder cancer   No prior or currently active autoimmune disease* requiring management with systemic immunosuppression, including any of the following:   Inflammatory bowel disease   Systemic vasculitis   Scleroderma   Psoriasis   Multiple sclerosis   Hemolytic anemia or immune-mediated thrombocytopenia   Rheumatoid arthritis   Systemic lupus erythematosus   Sjögren syndrome   Sarcoidosis   Other rheumatologic disease   No symptomatic intrinsic lung disease or extensive tumor involvement of the lungs resulting in dyspnea at rest   HIV-negative   No evidence of active acute or chronic infection   No uncontrolled medical problems   No active major medical or psychosocial problems that could be complicated by study participation   No corn allergy   No known severe hypersensitivity to trastuzumab (except for mild to moderate infusion reactions that are easily managed and do not recur) NOTE: *Asthma or chronic obstructive pulmonary disease that does not require daily systemic corticosteroids allowed   PRIOR CONCURRENT THERAPY:   Any number of prior chemotherapy regimens for metastatic breast cancer allowed   Prior or concurrent trastuzumab in the adjuvant or metastatic setting allowed   More than 28 days since prior and no concurrent systemic oral steroids   Topical, ocular, or nasal steroids allowed   More than 28 days since prior and no concurrent chemotherapy, radiotherapy, or biologic therapy (except trastuzumab)   More than 28 days since prior and no concurrent participation in another investigational clinical trial involving a new drug   Concurrent endocrine therapy or bisphosphonates allowed
Secondary_evidence: Inclusion Criteria:   Written informed consent and ability to follow the Protocol procedures;   Age from 18 years to 75 years inclusive;   Female gender;   Histologically confirmed breast cancer (BC);   Metastatic BC (stage IV according to TNM classification version 6);   Grade 3+ HER2 overexpression confirmed by immunohistochemical (IHC) staining or grade 2+ HER2 overexpression accompanied by HER2 gene amplification confirmed by fluorescent hybridization in situ (FISH) ;   Documented results of oestrogen and progesterone receptors expression analysis;   Eastern Cooperative Oncology Group (ECOG) status 0, 1 or 2, not increasing within 2 weeks prior to randomization;   Life expectancy - 20 weeks or more from the moment of randomization;   Presence of at least 1 tumour with a size not less than 1 cm (revealed with computed tomography (CT) slice thickness not more than 5 mm). Patients having bone metastasis as the only measurable tumour are not eligible for the trial;   Patients of childbearing potential must implement reliable contraceptive measures during the study treatment, starting 4 weeks prior to inclusion into the trial and until 6 months after the last administration of the study drug. Exclusion Criteria:   Previous anticancer therapy for metastatic BC, including cytotoxic chemotherapy, or previous anticancer therapy with signal transduction inhibitors (e.g. lapatinib), biological drugs (e.g. trastuzumab, bevacizumab), experimental (not approved for BC therapy) anticancer drugs. Any previous hormonal therapy is allowed;   Disease progression within 6 months after adjuvant and/or neoadjuvant anti BC therapy;   Surgery, radiation therapy, use of any experimental medications within 4 weeks (28 days) prior to randomization;   Hypersensitivity to paclitaxel and all medications containing polyoxyethylated castor oil, hypersensitivity to dexamethasone, diphenhydramine, ranitidine/cimetidine, recombinant murine proteins, contrast agents or excipients of study medications;   BC metastases in central nervous system, progressing or clinically manifested (e.g. cerebral oedema, spinal cord injury), with exception of non-progressing metastases not requiring treatment with glucocorticosteroids and/or anticonvulsants within 4 weeks prior to randomization;   Cardiovascular system pathology (congestive heart failure (CHF) stage III-IV according to New York Heart Association (NYHA) classification, unstable angina pectoris, myocardial infarction) within 12 months prior to randomization;   Uncontrolled hypertension comprising all cases of arterial hypertension when no decrease in blood pressure could be achieved despite treatment with a combination of 3 antihypertensive drugs including one diuretic and non-medicamental correction methods (low salt diet, physical exercise);   Left ventricular ejection fraction <50% according to electrocardiography;   Neutrophils 1500/mm3;   Platelets 100 000/mm3;   Hemoglobin 90 g/L;   Creatinine level  1.5 × upper limit of normal (ULN);   Bilirubin level  1.5 × ULN;   Asparagine transferase (AST) and alanine transferase (ALT) levels  2.5 × ULN (5 × ULN for patients with liver metastases);   Alkaline phosphatase level  5 × ULN;   Pregnancy or lactation;   Any other concomitant cancer including contralateral breast cancer revealed within 5 years prior to screening, except curatively treated intraductal carcinoma in situ, curatively treated cervical carcinoma in situ or curatively treated basal cell or squamous cell carcinoma;   Conditions limiting patient's adherence to protocol requirements (dementia, neurologic or psychiatric disorders, drug addiction, alcoholism and others);   Stage II-IV neuropathy according to Common Terminology Criteria for Adverse Events (CTCAE) v.4.0;   Concomitant participation in other clinical trials, previous participation in other clinical trials within 30 days before entering into the trial, previous participation in the same trial;   Acute or active chronic infections;   Hepatitis C virus, hepatitis B virus, HIV or syphilis infections;   Obstacles in intravenous administration of study drugs