Trastuzumab With or Without Everolimus in Treating Women With Breast Cancer That Can Be Removed By Surgery

Inclusion Criteria

• •DISEASE CHARACTERISTICS:
• •Histologically confirmed diagnosis of invasive breast cancer
• •* Previously untreated disease
• •Candidate for breast-conserving surgery, as defined by both of the following:
• •* Clinical stage cT1-3, cN0-2 disease
• •* Clinical stage M0 disease (bone scan, chest X-ray, and liver ultrasound required at screening to exclude metastatic disease)
• •HER2-positive primary tumor, defined as meeting either of the following criteria:
• •* IHC 3+
• •* IHC 2+ and FISH positive (centralized confirmation)
• •No inflammatory breast cancer or bilateral breast cancer
• •* Patients who have been treated for cancer of the contralateral breast can be included if there is at least a 5 year time interval from last systemic treatment for breast cancer before randomization into this study
• •Hormone receptor status not specified
• •PATIENT CHARACTERISTICS:
• •WHO performance status 0-1
• •Menopausal status not specified
• •WBC ≥ 3.5 x 10\^9/L
• •ANC ≥ 1.5 x 10\^9/L
• •Platelet count ≥ 100 x 10\^9/L
• •Hb ≥ 10 g/dL
• •Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
• •Serum transaminases activity ≤ 2.5 times ULN
• •Alkaline phosphatase ≤ 2.5 times ULN
• •Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
• •FEV \> 55% by MUGA or ECHO
• •Spirometry and DLCO \> 50% of normal
• •O\_2 saturation \> 88% at rest on room air
• •Not pregnant or nursing
• •Negative pregnancy test
• •Fertile patients must use effective contraception
• •No known hypersensitivity to everolimus, sirolimus, trastuzumab (Herceptin®), or lactulose
• •No hypercholesterolemia/hypertriglyceridemia ≥ grade 3
• •* No hypercholesterolemia/hypertriglyceridemia ≥ grade 2 with history of coronary artery disease (despite lipid-lowering treatment if given)
• •No uncontrolled infection
• •No other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, including any of the following:
• •* Uncontrolled hypertension
• •* Congestive cardiac failure
• •* Ventricular arrhythmias
• •* Active ischemic heart disease
• •* Myocardial infarction within the past year
• •* Chronic liver or renal disease
• •* Active gastrointestinal tract ulceration
• •* Severely impaired lung function
• •No known history of HIV seropositivity
• •No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• •Willing to participate in the biological investigations
• •Not deprived of liberty or placed under guardianship
• •Patients must be affiliated to a Social Security System
• •PRIOR CONCURRENT THERAPY:
• •See Disease Characteristics
• •More than 30 days (from the screening visit) since prior other investigational drugs
• •More than 5 days (from randomization) since prior and no concurrent strong inhibitors or inducers of the isoenzyme CYP3A, including any of the following
• •* Rifabutin
• •* Rifampicin
• •* Clarithromycin
• •* Ketoconazole
• •* Itraconazole
• •* Voriconazole
• •* Ritonavir
• •* Telithromycin
• •No other concurrent anti-cancer treatments such as chemotherapy, immunotherapy/biological response modifiers, endocrine therapy, or radiotherapy