Statement: the primary trial and the secondary trial use different inclusion criteria for their cohorts, so patients may be eligible for one cohort, but not the other.
Primary_evidence: Inclusion Criteria:   Patients with biopsy-confirmed breast cancer (prior histological documentation is acceptable).   Patients with measurable skin metastases (chest wall recurrence and/or non-chest wall skin metastases are eligible).   Skin metastases not suitable for or patient refusing definitive surgical resection and radiation.   (Cohort 1) Concurrent systemic cancer therapy (hormones, biologics or chemotherapy) is allowed if distant metastases have been non-progressing (stable or responding) on that regimen for > or = 12 weeks and skin metastases are non-responsive (stable or progressing) as assessed by the investigator.   (Cohort 2) Any concurrent systemic therapy is allowed   Age at least 18 years.   Eastern Cooperative Oncology Group (ECOG) performance status < or = 2.   Patients must have biopsy-accessible tumor (skin metastases) and agree to biopsies required by protocol.   Patients must have adequate organ and bone marrow function as defined below:   absolute neutrophil count > or = 1,500/microliter   hemoglobin > or = 9.5 grams/deciliter   platelets >or = 75,000/microliter   total bilirubin < or = 1.5 X institutional upper limit of normal   Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) < or = 2.5X institutional upper limit of normal   creatinine < or = 1.5 X institutional upper limit of normal   Informed consent. Exclusion Criteria:   Brain metastases unless resected or irradiated and stable > or = 8 weeks.   Treatment with other investigational agents.   Patients who have received radiotherapy, high-potency corticosteroids, intralesional therapy, laser therapy or surgery other than biopsy to the target area within 4 weeks prior to first dosing of study agent.   Patients who have received hyperthermia to the target area within 10 weeks prior to first dosing of study agent.   Patients with an uncontrolled bleeding disorder.   Patients who will be therapeutically anticoagulated with heparins or coumadin at the time of the biopsy (they are eligible if anticoagulation can be held prior to biopsy as per investigator). Patients on aspirin and other platelet agents are eligible.   Patients with known immunodeficiency or receiving immunosuppressive therapies.   History of allergic reactions to imiquimod or its excipients.   Uncontrolled intercurrent medical illness or psychiatric illness/social situations that would limit compliance with study requirements.   Pregnancy or lactation.   Women of childbearing potential not using a medically acceptable means of contraception.
Secondary_evidence: Inclusion Criteria:   Histologically or cytologically confirmed invasive breast carcinoma with locally recurrent or radiological evidence of metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.   HER2+ status defined as IHC 3+ staining or in situ hybridization positive   Patients with resistance to trastuzumab   Prior taxane therapy   Patients with an ECOG performance status of 0 - 2   Patients with measurable disease as per RECIST criteria   Documentation of negative pregnancy test for patients of child bearing potential prior to enrollment within 7 days prior to randomization. Sexually active pre-menopausal women must use adequate contraceptive measures, excluding estrogen containing contraceptives, while on study;   Patients must meet laboratory criteria defined in the study within 21 days prior to randomization Exclusion Criteria:   Prior mTOR inhibitors or vinca alkaloid agents for the treatment of cancer   More than three prior chemotherapy lines for advanced disease.   Symptomatic CNS metastases or evidence of leptomeningeal disease. Previously treated asymptomatic CNS metastases are allowed provided that the last treatment for CNS metastases was completed >8 weeks prior to randomization   Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus   Peripheral neuropathy  grade 2 at randomization   Active cardiac disease   History of cardiac dysfunction   Any malignancy within 5 years prior to randomization, with the exception of adequately treated in-situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer   Known hypersensitivity to any study medication   Breastfeeding or pregnant