Fulvestrant With or Without Lapatinib in Treating Postmenopausal Women With Stage III or Stage IV Breast Cancer That is Hormone Receptor-Positive

Exclusion Criteria

• •Tumors (as determined on pathology from either primary or metastatic sites) must be potentially sensitive to endocrine therapy, defined as expressing estrogen receptor (ER) and/or progesterone receptor (PgR) as determined immunohistochemical methods according to the local institution's standard protocol, \>= 1% cells will be considered to be positive
• •* Lesions that are considered non-measurable include the following:
• •* Bone lesions (women with bone lesions will be eligible as described above)
• •* Leptomeningeal disease
• •* Ascites
• •* Pleural/pericardial effusion
• •* Inflammatory breast cancer
• •* Lymphangitis cutis/pulmonitis
• •* Abdominal masses that are not confirmed and followed by imaging techniques
• •* Cystic lesions
• •Patients must have had one or two prior endocrine treatments for breast cancer in either the adjuvant or metastatic setting, exclusive of treatment-related amenorrhea or ovarian suppression; sequential use of two different third-generation aromatase inhibitors is considered "one" treatment; it is not required that tumors be resistant to such treatments; for example:
• •* A patient who received adjuvant tamoxifen and subsequent therapy with an aromatase inhibitor (adjuvant or metastatic) is eligible;
• •* A patient who received an aromatase inhibitor in either the adjuvant or metastatic setting, and who discontinued therapy after several months because of side effects, is eligible;
• •* A patient who received an aromatase inhibitor in the adjuvant setting is eligible, regardless of whether they did or did not receive tamoxifen at some point;
• •* A patient who received adjuvant tamoxifen, and subsequently a nonsteroidal aromatase inhibitor and a steroidal aromatase inhibitor for advanced breast cancer in the adjuvant or metastatic setting is eligible;
• •Tumors potentially sensitive to endocrine therapy, defined as \>= 3 months of prior endocrine therapy without disease progression in the adjuvant or metastatic setting
• •Patients must have had prior treatment in either the adjuvant or metastatic setting with a commercially available third-generation aromatase inhibitor (i.e. anastrozole, exemestane, or letrozole); it is not required that tumors be resistant to such therapies
• •Patients may have received up to one prior chemotherapy regimen for stage IV breast cancer; prior chemotherapy in the adjuvant and/or neoadjuvant setting is permitted; patients must have finished chemotherapy at least 1 week prior to starting protocol based treatment
• •Patients may have received prior trastuzumab therapy for stage IV breast cancer, in combination with up to one chemotherapy and/or endocrine therapy regimen, but that must have concluded at least 3 weeks prior to starting protocol-based therapy; prior trastuzumab therapy in the adjuvant and/or neoadjuvant setting is permitted, but must have concluded at least 3 weeks prior to starting protocol-based therapy
• •Prior therapy with commercially available inhibitor of EGFR (including but not limited to gefitinib, erlotinib, lapatinib or cetuximab) or experimental inhibitors of EGFR is prohibited
• •Patients may have initiated bisphosphonate therapy prior to study entry; such patients will have bone lesions considered evaluable for progression but not for response
• •Prior fulvestrant therapy is prohibited
• •Patients receiving a gonadotropin-releasing hormone (GnRH) agonist for ovarian suppression must remain on such therapy throughout the course of protocol treatment; patients must discontinue other endocrine treatments, including systemic hormone-replacement therapy and intravaginal estrogens prior to study entry; patients must have concluded radiation therapy prior to study entry; patients must be at least 1 week from prior chemotherapy or 3 weeks from prior trastuzumab therapy, with adequate recovery of bone marrow function and performance status
• •Patients must be postmenopausal women, defined as a woman fulfilling any of the following criteria:
• •* Age \>= 60 years; or
• •* Age \>= 45 years with an intact uterus and amenorrhea for 12 months or more; or
• •* History of bilateral oophorectomy; or
• •* Follicle stimulating hormone (FSH) levels within postmenopausal range according to the ranges established by the testing facility; or
• •* Treatment with a GnRH agonist for ovarian suppression for at least 3 consecutive months prior to study registration, and remaining on such therapy throughout the course of protocol treatment
• •Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-2
• •Absence of pending visceral crisis, in the opinion of the treating physician
• •Absence of acquired or inherited bleeding disorder
• •Absence of need for therapeutic systemic anticoagulation (defined as maintaining international normalized ratio \[INR\] \> 1.6); patients may take low-dose warfarin or aspirin (or equivalent) for maintenance of central venous catheter patency
• •Granulocytes \>= 1,000/μl
• •Platelet count \>= 100,000/μl
• •Creatinine =\< 2 mg/dl
• •Total bilirubin =\< 1.5 x upper limits of normal (ULN) unless due to Gilbert's syndrome
• •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN without liver metastases; =\< 5 x ULN with liver metastases
• •INR =\< 1.6
• •Left ventricular ejection fraction (LVEF) within institutional limits of normal