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

Inclusion Criteria

• •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