This clinical trial will study the use of ridaforolimus in metastatic breast cancer subjects whose tumors have shown a resistance to trastuzumab (herceptin). The goal of this study is to find out if subjects treated with ridaforolimus in combination with trastuzumab have a positive response to the treatment, and if treatment with ridaforolimus in combination with trastuzumab prolongs survival.

Inclusion Criteria:

• Female, 18 years of age or older
• Histologically confirmed HER2-positive metastatic breast cancer
• Trastuzumab-resistance
• Measurable disease, according to RECIST guidelines
• ECOG performance status less than or equal to 1
• Life expectancy greater than 3 months
• No prior treatment with temsirolimus, everolimus, rapamycin, or any other mTOR inhibitor
• At least 4 weeks must have lapsed between prior investigational therapy, chemotherapy or radiotherapy, and the first dose of ridaforolimus
• Left ventricular ejection greater than or equal to 50%
• Adequate cardiovascular function
• Adequate hematological, hepatic, and renal function
• Serum cholesterol less than or equal to 350 mg/dL and triglycerides less than or equal to 400 mg/dL
• Negative pregnancy test within 7 days prior to first dose of study drug and must use an approved contraceptive method from screening to 30 days after the last dose of study drug
• Availability and patient consent to obtain archival tissue samples
• Signed informed consent

Exclusion Criteria:

• Inadequate recovery from any prior surgical procedure or having undergone any major surgery within 2 weeks before trial entry
• Grade 1 or Grade 2 hypersensitivity reactions to prior trastuzumab therapy if these reactions prevented further trastuzumab administration
• Grade 3 or Grade 4 hypersensitivity reaction to prior trastuzumab
• Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs, resulting in dyspnea at rest
• Known allergy to macrolide antibiotics
• Pregnant or breast-feeding
• Know history of HIV
• Diagnosis of brain metastasis or leptomeningeal carcinomatosis within 3 months
• Other malignancies within the past 3 years, except for adequately treated carcinoma of the cervix or basal or squamous cell carcinoma of the skin
• Active infection requiring prescription intervention
• Newly diagnosed or poorly controlled Type 1 or 2 diabetes
• Other concurrent illness which, in the Investigator's judgment, would either compromise the patient's safety or interfere with the evaluation of the safety of the study drug
• Concurrent treatment with medications that strongly induce or inhibit cytochrome P450.
• Any condition that renders patient unable to fully understand and provide informed consent and/or comply with the protocol