Letrozole and Lapatinib Followed by Everolimus in Women With Advanced Breast Cancer

Inclusion Criteria: * Female greater than or equal to 18 years. * Histologically confirmed breast adenocarcinoma with incurable progressing local-regional or metastatic. * ER and/or PR positivity of primary and/or secondary tumor. * Patients must have measurable or evaluable disease. * Evidence of disease progression or relapse while on or less than 6 months off aromatase inhibitors or tamoxifen either in adjuvant or first line metastatic setting. * Postmenopausal * Patients may have received up to one prior chemotherapy regimen for stage IV breast cancer. Prior chemotherapy in the adjuvant and/or neoadjuvant setting is permitted. Chemotherapy must be finished at least 2 weeks prior to enrollment. * ECOG performance status \<2 * Fasting cholesterol ≤300 mg/dL OR ≤7.75 mmol/LAND fasting triglycerides ≤ 2.5 x ULN despite appropriate treatment. * Patients must have adequate organ function as defined by the protocol. * Stratification 1: * HER2 positive in the primary or secondary tumor tissue * Prior trastuzumab therapy is allowed but NOT required. However, trastuzumab should be discontinued at least 3 weeks prior to enrollment. * Stratification 2: * HER2 negative in the primary or secondary tumor tissue Exclusion Criteria: * Patients receiving any other investigational agents. * Prior exposure to lapatinib, everolimus, or other mTOR inhibitors. * History of allergic reactions or hypersensitivity to compounds similar to everolimus, lapatinib, or letrozole. * Patients who have any severe and/or uncontrolled medical conditions that could affect their participation such as: * Left ventricular ejection fraction (LVEF) \< 50% * Unstable angina, symptomatic congestive heart failure, myocardial infarction within 6 months, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease. * Severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is ≤ 88% at rest on room air. * Uncontrolled diabetes * Active or uncontrolled severe infection * Patients with QTc interval \> 0.47 seconds. * Significant chronic or acute gastrointestinal disorder with diarrhea as a major symptom. * Prior exposure to more than 360 mg/m2 doxorubicin, more than 120 mg/m2mitoxantrone, or more than 90 mg/m2idarubicin, or elevated baseline cardiac troponin I. * Patients with active CNS metastasis and/or carcinomatous meningtitis. However, patients with CNS metastasis who have completed a therapy and are clinically stable for 3 weeks as defined as: (1) no evidence of new or enlarging CNS metastasis and (2) off steroids and/or anticonvulsants. * Patient is known to be HIV, Hepatitis B, or Hepatitis C-positive (these tests are not required). * Patients with current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease). * Patients with INR ≥ 2 or PTT ≥ 2 x upper normal limit. * Previous or current systemic malignancy other than breast cancer within the past 3 years other than carcinoma in situ of the cervix or basal/squamous carcinoma of the skin.