Presurgical Therapy With Lapatinib to Explore Molecular Determinants of Response to EGFR/erbB2 Targeted Therapy

• Histologically or cytologically-confirmed by either core or fine needle biopsy primary invasive carcinoma of the breast;
• AJCC T2-T3 disease (>2.0 cm without chest wall or skin invasion) by at least one imaging modality (either mammogram, ultrasound, or MRI) - entry criteria is based on radiologic staging and not final pathologic staging;
• ECOG performance status 0-1 (Karnofsky ≥ 70%
• Any lymph node status, hormone receptor status, and level of erbB2 expression
• No prior chemotherapy, hormonal therapy or radiation therapy to the affected breast for current or previous malignancy;
• Cardiac ejection fraction >50% or within the institutional range of normal;
• Patients must have normal organ and marrow function defined as: Leukocyte count >3000/uL; Absolute neutrophil count (ANC) ≥ 1,500/mm3, platelets > 100,000/mm3, and hemoglobin ≥ 8 gm/dl; Serum creatinine ≤ 1.5 times ULN, or 24-hour creatinine clearance ≥ 75 cc/min; Serum bilirubin ≤ 1.5 times ULN; SGOT ≤ 2.5 times ULN; alkaline phosphatase ≤ 2.5 ULN times ULN.
• The effects of lapatinib on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Ability to understand and the willingness to sign written informed consent document.

Exclusion Criteria:

• AJCC T1, T4, or stage 4 disease;
• Patients may not have undergone incisional or excisional biopsy of their tumor;
• Patients may not be receiving any other investigational agents;
• Absolute contraindication to MRI imaging (cardiac pacemaker or any non-removable metallic foreign object in the body);
• On chronic therapy with any known inducer or inhibitor of CYP3A4
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or lactating women are excluded from this study because lapatinib is a tyrosine kinase inhibitor with the potential for teratogenic or abortifacient effects.