Doxorubicin and Cyclophosphamide Followed By Trastuzumab, Paclitaxel, and Lapatinib in Treating Patients With Early-Stage HER2-Positive Breast Cancer That Has Been Removed By Surgery

Inclusion Criteria

• •DISEASE CHARACTERISTICS:
• •Histologically confirmed diagnosis of early-stage breast cancer
• •* HER2 positive by immunohistochemistry (IHC) (3+) or fluorescent in situ hybridization (FISH)
• •* Ductal carcinoma in situ (DCIS) components should not be counted in the determination of degree of IHC staining or FISH amplification
• •No locally advanced tumors (i.e., T4) at diagnosis, including the following:
• •* Tumors fixed to chest wall
• •* Peau d'orange
• •* Skin ulcerations or nodules
• •* Clinical inflammatory changes (e.g., diffuse brawny cutaneous induration with an erysipeloid edge)
• •Has undergone mastectomy or lumpectomy with axillary node or sentinel node dissection within the past 84 days
• •* Patients who have undergone a mastectomy must meet the following criteria:
• •* No evidence of gross or microscopic tumor (i.e., invasive DCIS) at the surgical resection margins noted in final surgery or pathology reports
• •* Patients with close margins are eligible
• •* Radiation therapy is required for 4 or more positive lymph nodes and must be started after completion of chemotherapy
• •* Patients who have undergone a lumpectomy with axillary node or sentinel node dissection must meet the following criteria:
• •* No evidence of invasive cancer or DCIS at the surgical resection margins
• •* No gross residual adenopathy
• •* Planning to undergo radiation therapy to the breast with or without regional lymphatics after completion of chemotherapy
• •No active hepatic or biliary disease
• •* Patients with liver metastases, stable chronic liver disease, Gilbert's syndrome, or asymptomatic gallstones are eligible
• •Hormone receptor status:
• •* Estrogen receptor and progesterone receptor status known
• •PATIENT CHARACTERISTICS:
• •Male or female
• •Menopausal status not specified
• •ECOG performance status 0-2
• •Absolute neutrophil count ≥ 1,500/mm³
• •Platelet count ≥ 100,000/mm³
• •Hemoglobin ≥ 10.0 g/dL
• •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• •AST and ALT ≤ 2.5 times ULN
• •Alkaline phosphatase ≤ 2.5 times ULN
• •Creatinine normal OR creatinine clearance ≥ 60 mL/min
• •LVEF ≥ 50% by MUGA scan or echocardiogram
• •Able to complete questionnaire(s) by themselves or with assistance
• •Able and willing to provide blood and tissue samples
• •No known sensitivity to benzyl alcohol
• •No sensory neuropathy ≥ grade 2
• •No active cardiac disease, including any of the following:
• •* Myocardial infarction within the past 6 months
• •* Prior or concurrent congestive heart failure
• •* Prior or concurrent arrhythmia or cardiac valvular disease requiring medications or that is clinically significant
• •* Uncontrolled hypertension, defined as diastolic blood pressure (BP) \>100 mm Hg or systolic BP \> 200 mm Hg on 2 separate occasions ≥ 14 days apart
• •* Clinically significant pericardial effusion
• •* Prior or concurrent uncontrolled or symptomatic angina
• •* Other cardiac condition that, in the opinion of the treating physician, would put the patient at hazardous risk
• •No history of allergic reactions attributed to compounds of similar chemical or biologic composition as lapatinib ditosylate
• •No uncontrolled intercurrent illness including, but not limited to, the following:
• •* Ongoing or active infection
• •* Psychiatric illness or social situations that would preclude study compliance
• •Able to swallow and retain oral medication
• •* No history of gastrointestinal (GI) disease resulting in an inability to take oral medication, including any of the following:
• •* Malabsorption syndrome
• •* Requirement for IV alimentation
• •* Prior surgical procedures affecting absorption
• •* Uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)
• •Not pregnant or nursing
• •Negative pregnancy test
• •Fertile patients must use effective contraception during and for 6 months after completion of study treatment
• •PRIOR CONCURRENT THERAPY:
• •See Disease Characteristics
• •No prior chemotherapy, radiation therapy, immunotherapy, or biotherapy for breast cancer
• •No primary breast radiation therapy as part of breast-conserving treatment
• •No prior anthracycline or taxane therapy for any malignancy
• •No prior epidermal growth factor receptor-targeting therapies (e.g., gefitinib, cetuximab, erlotinib hydrochloride, rituximab, trastuzumab \[Herceptin®\], lapatinib ditosylate, panitumumab, or nimotuzumab)
• •At least 14 days since prior and no concurrent CYP3A4 inducers, including the following:
• •* Rifamycin-class antibiotics (e.g., rifampin, rifabutin, or rifapentine)
• •* Anticonvulsants (e.g., phenytoin, carbamazepine, or barbiturates \[e.g., phenobarbital\])
• •* Antiretrovirals (e.g., efavirenz or nevirapine)
• •* Glucocorticoids (e.g., oral cortisone, hydrocortisone, prednisone, methylprednisolone, or dexamethasone)
• •* Daily oral dexamethasone ≤ 1.5 mg (or equivalent) allowed
• •* Modafinil
• •* Hypericum perforatum (St. John's wort)
• •At least 7 days since prior and no concurrent CYP3A4 inhibitors, including the following:
• •* Antibiotics (e.g., clarithromycin, erythromycin, or troleandomycin)
• •* Antifungals (e.g., itraconazole, ketoconazole, fluconazole \[\> 150 mg daily\], or voriconazole)
• •* Antiretrovirals and protease inhibitors (e.g., delaviridine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, or lopinavir)
• •* Calcium channel blockers (e.g., verapamil or diltiazem)
• •* Antidepressants (e.g., nefazodone or fluvoxamine)
• •* Gastrointestinal agents (e.g., cimetidine or aprepitant)
• •* Grapefruit and grapefruit juice
• •At least 6 months since prior and no concurrent amiodarone
• •No herbal or alternative medicines or supplements ≥ 14 days before, during, and for 30 days after completion of study treatment
• •No concurrent hormonal agents (e.g., birth control pills, ovarian hormonal replacement therapy, or raloxifene)
• •* Adjuvant hormonal agents (e.g., tamoxifen, aromatase inhibitors) allowed after completion of chemotherapy as part of treatment for breast cancer
• •No concurrent antiretroviral therapy for HIV-positive patients
• •No concurrent digitalis or beta-blockers for congestive heart failure
• •No concurrent arrhythmia or angina pectoris medication
• •No other concurrent investigational agents or anticancer therapies, including cytotoxic agents or immunotherapy