Lapatinib and Tamoxifen in Treating Patients With Locally Advanced or Metastatic Breast Cancer That Did Not Respond to Previous Tamoxifen

Inclusion Criteria

• Primary adenocarcinoma of the breast confirmed by histology or cytology
• Locally advanced or metastatic disease not amenable to surgery or radiation therapy with curative intent
• Estrogen and/or progesterone receptor positive cancer
• Patients have failed hormonal manipulation with tamoxifen, either showing no response (primary resistance) to initial therapy or relapse/progression after showing initial response (secondary failure)
• At least 1 measurable (target) lesion (i.e. any malignant tumor mass that can be accurately measured in at least 1 dimension, >= 20 mm with conventional radiographic techniques or >= 10 mm with magnetic resonance imaging [MRI] or spiral computerized tomography [CT] scans), in a previously un-irradiated area
• No more than 450 mg/m^2 of prior doxorubicin
• Life expectancy >= 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status = = 60%)
• Absolute neutrophil count (ANC) >= 1500/mm^3
• Platelets >= 100,000/mm^3
• Hemoglobin >= 9.0 g/dL
• Creatinine (Cr) = 60 mL/min/m^2
• Total bilirubin =< 1.5 x ULN
• Alanine aminotransferase (ALT) =< 1.5 x ULN or =< 3 x ULN with liver metastases
• Aspartate aminotransferase (AST) =< 5 x ULN or =< 3 x ULN with liver metastases
• Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram or multi gated acquisition scan (MUGA) scan; (note that baseline and on-treatment scans should be performed using the same modality and preferably at the same institution)
• Patients on oral anticoagulants (Coumadin, warfarin) should either be switched to low molecular weight heparin or have a very close monitoring of international normalized ratio (INR), if continued on Coumadin
• Negative serum pregnancy test within 7 days of enrollment for pre-menopausal women and women within 6 months of menopause; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; both men and women should be counseled in contraceptive use due to unknown effects of the drug on the fetus and breast feeding should be avoided
• Ability to understand and the willingness to sign a written informed consent document
• Ability to swallow and retain oral medication

Exclusion Criteria

• Patients who have had prior treatment with EGFR and or Her-2 targeting therapies (prior trastuzumab combined with chemotherapy in the adjuvant setting only is allowed, but the combination of trastuzumab with hormonal therapy is not allowed)
• Current treatment with any other anti-neoplastic agent, including trastuzumab; patients may continue to receive zoledronic acid for bone metastases or hypercalcemia
• Radiation therapy within 2 weeks of enrollment or surgery within 4 weeks
• Rapidly progressive disease in major organs (i.e. lymphangitic spread, bulky liver metastasis) or known brain/leptomeningeal metastatic disease requiring active therapy; (patients with asymptomatic, stable previously treated metastases to the central nervous system and surrounding tissues are eligible; however patients must not have a requirement for corticosteroids due to central nervous system metastases at the time of study entry)
• Any of the following conditions within 6 months of enrollment: myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, coronary/peripheral artery bypass grafting; patients who have experienced a pulmonary embolus, deep venous thrombosis or other clinically significant thromboembolic event within 6 months of enrollment are eligible if they are clinically stable on anticoagulation therapy
• Pregnancy or breast feeding; breastfeeding should be discontinued if the mother is treated with GW572016; female patients must agree to use effective contraception during the study period, be surgically sterile, or be post-menopausal; in addition, male patients will be required to use effec