Docetaxel, Carboplatin, Trastuzumab, and Lapatinib in Treating Patients With Early Stage Breast Cancer

DISEASE CHARACTERISTICS:

• Histologically confirmed primary invasive adenocarcinoma of the breast fulfilling the following criteria:

  • Nonmetastatic disease

  • Operable and adequately excised

    • Patients with nonresectable deep margin invasion are eligible provided they have had or will receive radiotherapy to the region
    • Patients with histologically documented infiltration of the skin (pT4) are eligible provided they have undergone or will receive radiotherapy encompassing the tumor bed
  • Node-positive OR -negative and determined eligible to receive adjuvant trastuzumab (Herceptin®)
• No positive or suspicious internal mammary nodes by SNS that have not been or will not be irradiated
• No supraclavicular lymph node involvement (confirmed by fine needle aspiration or biopsy)

• Over expression and/or amplification of HER2 in the invasive component of the primary tumor, according to one of the following:

  • 3+ over-expression by IHC (> 30% of invasive tumor cells)
  • 2+ or 3+ (in 30% or less neoplastic cells) over-expression by IHC AND in situ hybridization (FISH/CISH) test demonstrating HER2 gene amplification

  • HER2 gene amplification by FISH/CISH (> 6 HER2 gene copies per nucleus, or a FISH ratio [HER2 gene copies to chromosome 17 signals] of > 2.2.)

    • Negative or equivocal overall result (FISH test ratio of < 2.2, < 6.0 HER2-gene copies per nucleus) and staining scores of 0, 1+, 2+, or 3+ (in 30% or less neoplastic cells) by IHC not allowed
• Hormone receptor status known (estrogen receptor with or without progesterone receptor)

PATIENT CHARACTERISTICS:

• Menopausal status not specified
• ECOG performance status 0-1
• Hemoglobin ≥ 10.0 g/dL
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Serum creatinine ≤ 2.0 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• Bilirubin ≤ 1.5 times ULN (≤ 2.0 times ULN if known Gilbert syndrome)
• Baseline LVEF ≥ 50% measured by ECHO or MUGA scan
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

• No serious cardiac illness or medical condition including, but not limited to, any of the following:

  • History of documented congestive heart failure (any NYHA class) or systolic dysfunction (LVEF < 50%)
  • High-risk uncontrolled arrhythmias (e.g., ventricular tachycardia, high-grade atrioventricular-block [second degree or higher], or supraventricular arrhythmias that are not adequately rate-controlled)
  • Angina pectoris requiring antianginal medication
  • Clinically significant valvular heart disease
  • Evidence of transmural infarction on ECG
  • Poorly controlled hypertension (any reading of systolic BP > 180 mm Hg or diastolic BP > 100 mm Hg)
• No other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions or illness

• None of the following:

  • Ulcerative colitis
  • Malabsorption syndrome
  • Any disease significantly affecting gastrointestinal function
  • Inability to swallow oral medication

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior mediastinal irradiation except internal mammary-node irradiation for the present breast cancer
• No prior anti-HER2 therapy for any reason
• No prior biologic or immunotherapy for breast cancer
• No prior resection of the stomach or small bowel
• No other concurrent anticancer therapy including chemotherapeutic agents, biologic agents, or radiotherapy
• No concurrent anticancer treatment in another investigational trial with hormone therapy or immunotherapy unless approved by the study chair
• No concurrent CYP3A4 inhibitors or inducers
• No concurrent epoetin alfa, including darbepoetin alfa
• No concurrent oprelvekin