Influence of Exceptional Patient Characteristics on Everolimus Exposure

Inclusion criteria

• Adult women (≥ 18 years of age) with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.
• Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer
• Postmenopausal women
• Radiological or clinical evidence of recurrence or progression on last systemic therapy prior to enrollment.
• Progression following a non-steroidal aromatase inhibitor
• Falling into one of the following categories

• elderly patients (age ≥ 70 years and BMI < 30 kg/m2); or
• obese patients (BMI ≥ 30 kg/m2 and age < 70 years); or
• control patients (BMI < 30 kg/m2 and age < 70 years);
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 x ULN
• Adequate renal function: calculated creatinine clearance, as estimated by GFR using the MDRD formula, is ≥ 30ml/min/1.73m2
• Performance status ECOG 0 - 2 (Karnofsky index: 60 - 100)
• Patient is willing and able to sign the Informed Consent Form prior to screening evaluations

Exclusion criteria

• Patients aged ≥ 70 years AND BMI ≥ 30 kg/m2
• HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
• Previous treatment with exemestane or mTOR inhibitors. Except for the treatment with exemestane in the adjuvant setting.
• Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin).
• Patients with a known history of HIV seropositivity.
• Any severe and / or uncontrolled medical conditions such as:

• Unstable angina pectoris, serious uncontrolled cardiac arrhythmia
• Patients with severe hepatic impairment (Child-Pugh A/B/C)
• Uncontrolled diabetes mellitus
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
• Patients who test positive for hepatitis B or C
• Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A within the last 5 days prior to enrollment
• History of non-compliance to medical regimens
• Patients unwilling to or unable to comply with the protocol