Statement: Patients wanting to take part in the secondary trial must be at a specific location, this is not necessary for the primary trial.
Primary_evidence: Eligibility Criteria:   Patients must be women with a histologically confirmed diagnosis of locally advanced or inflammatory breast carcinoma. Histologic confirmation shall be by either core needle biopsy or incisional biopsy. Punch biopsy is allowed if invasive breast cancer is documented.   Patients must meet one of the criteria defined below (indicate one):   a .Selected Stage IIB (T3, N0, M0) or IIIA (T3, N1-2, M0) disease judged primarily unresectable by an experienced breast surgeon; or otherwise deemed appropriate candidates for neoadjuvant treatment.   b. Stage IIIB (T4, Any N, M0) or (Any T, N3, M0) disease.   Physical examination, chest x-ray and any x-rays or scans needed for tumor assessment must be performed within 90 days prior to registration.   Patients with the clinical diagnosis of congestive heart failure or angina pectoris are NOT eligible. Patients with hypertension or age > 60 years must have a Multiple Gated Acquisition (MUGA) or echocardiogram scan performed within 90 days prior to registration (indicate not applicable (NA) if no MUGA required) and Left Ventricular Ejection Fraction (LVEF) % must be greater than the institutional lower limit of normal.   Patients must have a serum creatinine and bilirubin  the institutional upper limit of normal, and an Serum glutamic oxaloacetic transaminase (SGOT) or Serum glutamic pyruvic transaminase (SGPT)  2x the institutional upper limit of normal. These tests must have been performed within 90 days prior to registration.   Patients must have an Absolute neutrophil count (ANC) of  1,500/μl and a platelet count of  100,000/μl. These tests must have been performed within 90 days prior to registration.   Patients must have a performance status of 0-2 by Zubrod criteria   Pregnant or nursing women may not participate due to the possibility of fetal harm or of harm to nursing infants from this treatment regimen. Women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. A urine pregnancy test is required for women of childbearing potential.   All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
Secondary_evidence: Inclusion Criteria:   Patients with a diagnosis of invasive adenocarcinoma of the breast confirmed by histology or cytology at MSKCC.   Clinical evidence of metastatic breast cancer.   HER2 overexpression and/or amplification as determined by immunohistochemistry (3+) or FISH (  2.0).   Progressive disease following treatment with trastuzumab for metastatic breast cancer or as adjuvant therapy (either single-agent or combination therapy)   Prior therapy inclusion:   No more than two prior chemotherapy regimens allowed for advanced stage disease   No prior fluoropyrimidine in the metastatic setting. Adjuvant fluoropyrimidine is permitted if >6 months prior to treatment on study.   No restriction for prior hormonal therapy. No concurrent use of endocrine therapy is permitted.   No more than 450mg/m2 cumulative dose of prior doxorubicin   At least 3 weeks since prior chemotherapy or radiation therapy   Age  or = to 18. Because no dosing or adverse event data are currently available on the use of lapatinib in patients <18 years of age, children are excluded from this study.   Patients must be willing to discontinue sex hormonal therapy e.g., birth control pills, ovarian hormonal replacement therapy, etc., prior to enrollment. Women of childbearing potential must be willing to consent to using effective contraception while on treatment and for a reasonable period thereafter.   Negative HCG pregnancy test for premenopausal women of reproductive capacity and for women less than 12 months after the menopause.   Asymptomatic, central nervous system metastases are permitted if patients remain clinically stable after discontinuation of corticosteroids and anticonvulsants.   ECOG performance status < or = to 2   Life expectancy of greater than 12 weeks   Patients must have normal organ and marrow function as defined below:   leukocytes  or = to 3,000/μL   absolute neutrophil count  or = 1,500/μL   platelets  or = 100,000/μL   total bilirubin within normal institutional limits AST (SGOT)/ALT(SGPT)  or = 2.5x institutional upper limit of normal serum creatinine within normal institutional limits   Cardiac ejection fraction at or above the lower limit of normal of 50% as measured by multigated radionuclide angiography (MUGA) scan. If LVEF is greater than 70%, and ECHO should be performed as well. Baseline and on treatment scans should be performed using the same modality and preferably at the same institution.   Ability to understand and the willingness to sign a written informed. consent document.   Able to swallow and retain oral medication. Exclusion Criteria:   Patients may not be receiving any concurrent anticancer therapy or investigational agents with the intention of treating breast cancer.   History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib or capecitabine.   Known DPD deficiency.   Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within 6 months of study entry, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.   Pregnant women are excluded from this study because lapatinib is member of the 4- anilinoquinazoline class of kinase inhibitors with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lapatinib, breastfeeding should be discontinued if the mother is treated with lapatinib.   HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with lapatinib. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.   Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption,uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis).   Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors:   Medications that inhibit or induce CYP3A4 are prohibited. Eligibility of patients receiving medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of lapatinib will be determined following review of their use by the Principal Investigator.   Renal function as measured by creatinine clearance < 30ml/min   Patients are permitted to participate in other non-therapeutic clinical trials while receiving treatment on this study (ie, experimental imaging, minor procedures necessary for tissue acquisition on study)