Everolimus, Letrozole and Trastuzumab in HR- and HER2/Neu-positive Patients

PRIMARY OBJECTIVES: I. Determine reasonable dose of drugs in treatment combination, including maximum tolerated dose (MTD) and toxicity profiles, via a brief initial "run-in"/dose escalation. II. Evaluate response, in patients with tumors that demonstrate hormone receptor (HR)-positivity (\> 1% on immunohistochemistry \[IHC\]) and human EGF receptor 2 (HER)-positivity (IHC 3 and/or IHC 2/3 and fluorescence in situ hybridization \[FISH\] amplification). SECONDARY OBJECTIVES: I. Correlate activity of combination with genomic and proteomic signatures. II. Evaluate 2 expanded cohorts of patients to include: 1) HR- and HER2-positive breast cancer (n=12) and 2) other HR- and HER2-positive tumors that have demonstrated activity in the dose escalation portion of the study (n=12). OUTLINE: This is a dose-escalation study of everolimus and trastuzumab. Patients receive everolimus orally (PO) once daily (QD) and letrozole PO QD. Patients also receive trastuzumab intravenously (IV) over 30-90 minutes once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for at least 30 days.