Fulvestrant With or Without AZD6244 in Treating Patients With Advanced Breast Cancer That Progressed After Aromatase Inhibitor Therapy

DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed breast cancer

  * Not amenable to curative therapy
* HER-2 positive disease allowed
* Disease relapse or progression after aromatase inhibitor as adjuvant therapy or for advanced stage disease
* Bilateral breast cancer allowed provided tumor endocrine sensitivity has been proven on both sides
* Measurable disease according to RECIST criteria v1.1 or other lesions assessable by radiological exams (i.e., bone-only disease or small but unequivocal liver or lung metastases)
* Received no more than 1 line of chemotherapy for advanced stage disease
* Estrogen receptor- and/or progesterone receptor-positive (≥ 10% tumor cells positive by immunohistochemistry or ≥ 10 fmol/mg cytosol protein by ligand binding assay)
* No known CNS metastases

  * Patients with brain metastases treated with radiotherapy and without any sign of brain progression after ≥ 3 months since the end of radiotherapy may be considered eligible after trial chair approval)

PATIENT CHARACTERISTICS:

* WHO performance status 0-2
* Postmenopausal
* Hemoglobin ≥ 90 g/L
* Platelet count ≥ 100 x 10\^9/L
* Absolute neutrophil count ≥ 1.5 x 10\^9/L
* Creatinine clearance ≥ 30 mL/min
* ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN in patients with liver metastases)
* Bilirubin ≤ 1.5 times ULN
* INR \< 1.6
* PTT normal
* LVEF ≥ 50%
* Able to swallow AZD6244/placebo capsules
* Capable of understanding information given by the investigator on the trial
* Must adhere to and be geographically proximal to allow for proper staging, treatment, and follow up
* No contraindication for intramuscular injections
* No bleeding diathesis
* No current or prior malignancy other than breast cancer within the past 5 years, except carcinoma in situ of the cervix or basal cell carcinoma of the skin treated curatively
* No serious underlying medical condition that, in the judgment of the investigator, would impair the ability of the patient to participate in the trial (e.g., active autoimmune disease or uncontrolled diabetes)
* No refractory nausea and vomiting, chronic gastrointestinal disease (e.g., inflammatory bowel disease), or significant bowel resection that preclude adequate absorption
* No psychiatric disorder precluding understanding of information on trial-related topics, giving informed consent, or interfering with adherence for oral drug intake
* No uncontrolled hypertension (systolic BP \> 150 mm Hg and/or diastolic BP \> 100 mm Hg, measured repeatedly at more than two visits despite adequate treatment with at least two different antihypertensive drugs)
* No clinically significant (i.e., active) cardiovascular disease, including any of the following:

  * Cerebrovascular accident/stroke or myocardial infarction within the past 6 months
  * Unstable angina
  * NYHA class III-IV congestive heart failure
  * Serious cardiac arrhythmia or AV-block \> 1, requiring medication during the trial and which might interfere with regularity of the trial treatment, or not controlled by medication
* No known hypersensitivity to trial drugs or any other component of the trial drugs

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* At least 30 days since other prior experimental drugs or participation in another clinical trial
* No prior fulvestrant, AZD6244, MEK inhibitors, RAF inhibitors, or endocrine therapies other than aromatase inhibitors (e.g., anastrazole, letrozole, or exemestane) or tamoxifen
* No more than 1 line of aromatase inhibitors (steroidal and nonsteroidal aromatase inhibitors are considered two different lines)
* No concurrent full-dose anticoagulation therapy (e.g., low molecular weight heparin, acenocoumarol, phenprocoumon, or analogues)

  * Prophylactic doses of anticoagulation or antiplatelet may be allowed
* No concurrent radiotherapy
* No other concurrent anticancer therapy or experimental drugs
* Concurrent bisphosphonate allowed provided the investigator rules out tumor progression