- Female gender;
- Age 18 years;
- Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1
- Histologically confirmed invasive breast cancer:
- Primary tumor greater than 1 cm diameter, measured by clinical examination and
mammography or ultrasound.
- Any N,
- No evidence of metastasis (M0) (isolated supra-clavicular node involvement allowed);
- Over expression and/or amplification of HER2 in the invasive component of the primary
tumor and confirmed by a certified laboratory prior to randomization.
- Known hormone receptor status.
- Hematopoietic status:
- CBC not less than .75 of institutional lower limit. Absolute neutrophil count 1,5 x
10^9/L, Platelet count 100 x 10^9/L, Hemoglobin at least 9 g/dl,
- Hepatic status:
Serum total bilirubin 2 x upper limit of normal (ULN). In the case of known Gilbert's
syndrome, a higher serum total bilirubin (< 1.5 x ULN) is allowed, Aspartate
Aminotransferase (AST) and Alanine Aminotransferase (ALT) 3.5 times ULN, Alkaline
phosphatase 2.5 times ULN, Renal status: Creatinine 1.5mg/dL,
Cardiovascular: Baseline left ventricular ejection fraction (LVEF) 50% measured by
echocardiography (ECHO) or Multiple Gate Acquisition (MUGA) scan,
- Negative serum or urine -hCG pregnancy test at screening for patients of
childbearing potential within 2-weeks (preferably 7 days) prior to randomization.
- Fertile patients must use effective contraception (barrier method - condoms,
diaphragm - also in conjunction with spermicidal jelly, or total abstinence. Oral,
injectable, or implant hormonal contraceptives are not allowed)
- Signed informed consent form (ICF)
- Patient accepts to make available tumor samples for submission to central laboratory
to conduct translational studies as part of this protocol.
- Previous (less than 5 years) or current history of malignant neoplasms, except for
curatively treated: Basal and squamous cell carcinoma of the skin; Carcinoma in situ
of the cervix.
- Patients with a prior malignancy diagnosed more than 5 years prior to randomization
may enter the study.
- Preexisting peripheral neuropathy grade 2
- Known history of uncontrolled or symptomatic angina, clinically significant
arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled
hypertension (180/110), unstable diabetes mellitus, dyspnea at rest, or chronic
therapy with oxygen;
- Concurrent disease or condition that would make the subject inappropriate for study
participation or any serious medical disorder that would interfere with the subject's
- Unresolved or unstable, serious adverse events from prior administration of another
- Dementia, altered mental status, or any psychiatric condition that would prevent the
understanding or rendering of ICF;
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
resection of the stomach or small bowel. Subjects with ulcerative colitis are also
- Concurrent neoadjuvant cancer therapy (chemotherapy, radiation therapy,
immunotherapy, biologic therapy other than the trial therapies);
- Concurrent treatment with an investigational agent or participation in another
therapeutic clinical trial;
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to trastuzumab Emtansine, trastuzumab, lapatinib, paclitaxel,
abraxane or their components;
- Pregnant or lactating women;
- Concomitant use of CYP3A4 inhibitors or inducers
- Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.
active or uncontrolled infection, uncontrolled diabetes) that could cause
unacceptable safety risks or compromise compliance with the protocol
- Patients have an active infection and require IV or oral antibiotics.
- Pregnant or breast-feeding women
- Patients unwilling or unable to comply with the protocol
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Female