Inclusion Criteria:

• Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the investigational product that may impact patient eligibility is provided in the pazopanib IB and IB supplement and lapatinib product label.
• Patients eligible for enrollment in the study must meet all of the following criteria:
• Histological confirmation of breast carcinoma with a clinical diagnosis of IBC at original diagnosis based on the presence of inflammatory changes in the involved breast, including diffuse erythema and edema (peau d'orange), with or without an underlying palpable mass. Pathologic evidence of dermal lymphatic invasion should be noted but is not required for diagnosis. Documentation of initial diagnosis of IBC must be included in source documentation.
• Disease progression or relapse following treatment for IBC, which must have included a chemotherapy regimen. In regions where trastuzumab is available with no barriers to access, patients must have received prior trastuzumab in addition to chemotherapy in order to be eligible.
• Tumor that overexpresses ErbB2 as defined by at least one of the following based on local results: 1.) 3+ overexpression by IHC or 2.) HER2 gene amplification by FISH or CISH. Archived tumor tissue must be provided for all patients for ErbB2 FISH testing by the central laboratory. Central testing is for analysis only. Patients will remain on study based on local ErbB2 expression results.
• Patients will have radiographically measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) [Therasse, 2000] or evaluable IBC cutaneous disease. If the only evidence of recurrent IBC is cutaneous disease, the cutaneous disease must have been biopsied at some time.
• Radiographically measurable lesions may be in the field of prior adjuvant irradiation; however, there must be at least an 8 week period between the last radiation treatment and the baseline scan documenting disease status for the lesion to be measurable. If the irradiated lesion is the only site of disease, documented progression of the irradiated lesion is required.
• Patients must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up. Procedures conducted as part of the patient's routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol.

Note: It is not necessary that informed consent be obtained within the protocol-specified screening window.

• Age ≥ 18 years.
• Adequate organ function as defined in Table 1 below:

Table 1 Definitions for Adequate Organ Function:

• System (Laboratory Values)
• Hematologic:Absolute neutrophil count (ANC)(≥ 1.5 X 10^9/L)Hemoglobin1(≥9 g/dL)Platelets(≥100 X 10^9/L)International normalized ratio (INR)(≤ 1.2 X upper limit of normal (ULN))Partial thromboplastin time (PTT)(≤1.2 X ULN)
• Hepatic:Total bilirubin (≤ 1.5 X upper limit of normal (ULN))AST and ALT(≤ 2.5 X ULN)
• Renal:Serum Creatinine (≤ 1.5 mg/dL)Or, if serum creatinine >1.5 mg/dL,
• Calculated creatinine clearance(≥50 mL/min)

• Urine Protein to Creatinine Ratio2(<1)

  1. Patients may not have had a transfusion within 7 days of screening assessment.
  2. If UPC ≥ 1, then a 24-hour urine protein must be assessed. Patients must have a 24-hour urine protein value <1g to be eligible.
• Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram. MUGA scans will be accepted in cases where an echocardiogram cannot be performed or is inconclusive or where MUGA scans are the accepted standard. Patients with known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure are not eligible.
• Archived tumor tissue must be provided for all patients.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• A female is eligible to enter and participate in this study if she is of:
• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had:
• A hysterectomy
• A bilateral oophorectomy (ovariectomy)
• A bilateral tubal ligation
• Is post-menopausal

Patients not using hormone replacement therapy (HRT) must have experienced total cessation of menses for ≥ 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value >40 mIU/mL and an estradiol value < 40pg/mL (<140 pmol/L).

Patients must discontinue HRT prior to study enrollment due to the potential for inhibition of CYP enzymes that metabolize estrogens and progestins (See Section 8). For most forms of HRT, at least 2-4 weeks must elapse between the cessation of HRT and determination of menopausal status; length of this interval depends on the type and dosage of HRT. If a female patient is determined not to be post-menopausal, they must use adequate contraception, as defined immediately below.

Childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, has used adequate contraception since the pregnancy test and agrees to use adequate contraception as described below. GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow:

• An intrauterine device with a documented failure rate of less than 1% per year.
• Vasectomized partner who is sterile prior to the female patient's entry and is the sole sexual partner for that female.
• Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product.
• Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide).

Note: Oral contraceptives are not reliable due to potential drug drug interactions.

Female patients who are lactating should discontinue nursing prior to the first dose of investigational product and should refrain from nursing throughout the treatment period and for 14 days following the last dose of investigational product.

• French patients: In France, a patient will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

• Patients meeting any of the following criteria must not be enrolled in the study:
• Treatment in the 14 days prior to randomization with any cancer therapy (surgery, tumor embolization, chemotherapy, radiation therapy, immunotherapy, biological therapy, or hormonal therapy) or treatment with mitomycin within 6 weeks prior to randomization. Such treatment may not be resumed or begun after study entry. Note: Patients receiving LH-RH analogue therapy prior to the study may continue to receive LH-RH analogues for the duration of study participation.
• Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity.
• Prior lapatinib therapy.
• Use of an investigational agent, including an investigational anti-cancer agent, within 28 days or 5 half-lives, whichever is longer, prior to the first dose of investigational product.
• Use of any prohibited medication within the timeframes listed in Section 8.2.
• Evidence of recurrence or active disease from prior malignancy.
• History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 2 months prior to first dose of study drug. Screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases.
• Clinically significant gastrointestinal abnormalities that may increase the risk for GI bleeding including, but not limited to:
• Active peptic ulcer disease
• Inflammatory bowel disease
• Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation
• History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
• Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but limited to:
• Malabsorption syndrome
• Major resection of the stomach or small bowel.
• Presence of uncontrolled infection.
• Prolongation of corrected QT interval (QTc) > 480 msecs.
• History of any one or more of the following cardiovascular conditions within the past 6 months:
• Cardiac angioplasty or stenting
• Myocardial infarction
• Unstable angina
• Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA).
• Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg].

Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Blood pressure must be re-assessed on two occasions that are separated by a minimum of 24 hours. The mean SBP / DBP values from each blood pressure assessment must be < 140/90mmHg in order for a patient to be eligible for the study. See Sections 6.2 and 6.4.2 for details on blood pressure control and reassessment prior to study enrollment.

• History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.

Note: Patients with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible.

• Prior major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer
• Evidence of active bleeding or bleeding diathesis.
• Hemoptysis within 6 weeks prior to first dose of investigational product.
• Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with patient's safety, provision of informed consent, or compliance to study procedures.
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or lapatinib.