This study will characterize the effect of elevated gastric pH mediated by the proton-pump inhibitor, esomeprazole, on the relative bioavailability of lapatinib in subjects with metastatic ErbB2 positive breast cancer.

Inclusion Criteria:

• Metastatic, histologically confirmed breast cancer that overexpresses ErbB2 (3+ by IHC, FISH, or CISH positive).
• 18 years to 65 years of age.
• Is male or female (of non childbearing potential or willing to use contraception as specified in the protocol).
• Is able to swallow and retain oral medication.
• ECOG performance status 0 to 2.
• Provided written informed consent.
• Adequate bone marrow function (as specified in the protocol).
• Calculated creatinine clearance (CrCl) greater than or equal to 50 ml/min based on Cockcroft and Gault.
• Total bilirubin less than or equal to 1.5 X upper limit of normal of institutional values.
• Alanine transaminase (ALT) less than or equal to 3 times the upper limit of the institutional values or less than or equal to 5 times ULN with documented liver metastases
• Has a left ventricular ejection fraction (LVEF) within the normal institutional range based on ECHO or MUGA.
• Life expectancy of greater than or equal to 12 weeks
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

• Pregnant or lactating woman.
• Has malabsorption syndrome, a disease affecting gastrointestinal function, or resection of the stomach or small bowel.
• Has current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
• Has evidence of symptomatic or uncontrolled brain metastases or leptomeningeal disease. Subjects with brain metastases treated by surgery and/or radiotherapy are eligible if neurologically stable and do not require steroids or anticonvulsants.
• Is considered medically unfit for the study by the investigator.
• Has a known immediate or delayed benzimidazole hypersensitivity reaction or idiosyncrasy to drugs chemically related to the investigational product such as gefitinib [Iressa] and erlotinib [Tarceva].
• Has received treatment with any investigational drug in the previous four weeks. (with the exception of lapatinib).
• Has received chemotherapy, immunotherapy, biologic therapy or hormonal therapy for the treatment of cancer within the past 14 days, with the exception of mitomycin C which is restricted for the past six weeks, and lapatinib. Subjects receiving lapatinib prior to study entry are eligible to participate in the study.
• Is receiving any prohibited medication within the timeframe indicated on the prohibited medication list in the protocol.
• Has physiological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
• Has inadequate venous access for protocol-related blood draws.
• Clinically significant electrocardiogram abnormality.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or kumquats, pummelos, exotic citrus fruit (i.e. star fruit, bitter melon), grapefruit hybrids or fruit juices from seven days prior to the first dose of study medication.