Fulvestrant With or Without Lapatinib and/or Aromatase Inhibitor Therapy in Treating Postmenopausal Women With Metastatic Breast Cancer That Progressed After Previous Aromatase Inhibitor Therapy

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed breast cancer
• Metastatic disease
• Confirmed disease progression after treatment with an aromatase inhibitor (AI) administered in the adjuvant or metastatic setting
• Must have demonstrated a prior response to AI therapy (i.e., responded after > 2 years of treatment in the adjuvant setting OR complete or partial response or stable disease after ≥ 24 weeks of treatment in the metastatic setting) AND have subsequent disease progression after completion of AI therapy
• Meets 1 of the following criteria:
• Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or ≥ 10 mm with spiral CT scan
• Evaluable disease, defined as bone lesions, lytic or mixed (lytic and sclerotic), evaluable by plain x-ray, CT scan, or MRI
• Lesions identified only by radionucleotide bone scan are not allowed
• No HER2/neu-overexpressing tumor (IHC 3+ or FISH+)
• Hormone receptor status:
• Estrogen receptor- and/or progesterone receptor-positive primary or metastatic tumor

PATIENT CHARACTERISTICS:

• Female
• Postmenopausal, as defined by any of the following criteria:
• At least 60 years of age
• 45 to 59 years of age and meets ≥ 1 of the following criteria:
• Amenorrhea for ≥ 12 months and intact uterus
• Amenorrhea for < 12 months and follicle-stimulating hormone within the postmenopausal range (including patients with hysterectomy, prior hormone replacement therapy, or chemotherapy-induced amenorrhea)
• Patients who received prior luteinizing hormone-releasing hormone (LHRH) analogues must not have restarted their menses after cessation of therapy
• Over 18 years of age and bilateral oophorectomy
• WHO performance status 0-2
• Life expectancy ≥ 8 months
• Leukocytes ≥ 3,000/μL
• Absolute neutrophil count ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Total bilirubin normal
• AST/ALT ≤ 2.5 times upper limit of normal
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• LVEF normal as measured by ECHO or MUGA
• Able to swallow and retain oral medication
• No ulcerative colitis
• No malabsorption syndrome or disease significantly affecting gastrointestinal function
• No known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure
• No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to fulvestrant, aromatase inhibitors, lapatinib tosylate, or excipients
• No unresolved or unstable serious toxicity from prior therapy
• No active or uncontrolled infection
• No dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent
• No other malignancy within the past 5 years except for adequately treated cervical carcinoma in situ, melanoma in situ, or basal cell or squamous cell carcinoma of the skin
• No other concurrent disease or condition that would make the patient inappropriate for study participation
• No serious medical disorder that would interfere with patient safety

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Prior radiotherapy for the primary or metastatic tumor allowed
• More than 4 months since prior LHRH analogues
• More than 30 days (or 5 half-lives, whichever is longer) since prior investigational agents
• More than 14 days since prior and no concurrent CYP3A4 inducers*, including any of the following:
• Rifampin, rifapentine, rifabutin, or other rifamycin class agents
• Phenytoin, carbamazepine, or barbiturates (e.g., phenobarbital)
• Efavirenz or nevirapine
• Oral glucocorticoids (e.g., cortisone [> 50 mg], hydrocortisone [> 40 mg], prednisone [> 10 mg], methylprednisolone [> 8 mg], or dexamethasone [> 1.5 mg])
• Modafinil
• More than 14 days since prior and no concurrent herbal or dietary supplements*, including any of the following:
• St. John's wort
• Ginkgo biloba
• Kava
• Grape seed
• Valerian
• Ginseng
• Echinacea
• Evening primrose oil
• More than 7 days since prior and no concurrent CYP3A4 inhibitors*, including any of the following:
• Clarithromycin, erythromycin, or troleandomycin
• Itraconazole, ketoconazole, fluconazole (> 150 mg daily), or voriconazole
• Delaviridine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, or lopinavir
• Verapamil or diltiazem
• Nefazodone or fluvoxamine
• Cimetidine or aprepitant
• Grapefruit or grapefruit juice
• More than 6 months since prior and no concurrent amiodarone*
• No prior fulvestrant and/or lapatinib tosylate
• No prior resection of the stomach or small bowel
• No other concurrent anticancer therapy, including chemotherapy, immunotherapy, and biologic therapy
• Concurrent bisphosphonates allowed
• No other concurrent investigational therapy
• No concurrent participation in another clinical trial NOTE: *For patients randomized to receive lapatinib