Phase 2, Endocrine Therapy + OSI-906 With or Without Erlotinib for Hormone-sensitive Metastatic Breast Cancer

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive breast carcinoma
• Stage IV disease
• No locally recurrent resectable disease
• No symptomatic brain metastases
• History of brain metastases allowed provided the patient is clinically stable for > 3 weeks after completion of radiotherapy AND is not taking steroids or therapeutic anticonvulsants that are CYP3A4 modifiers
• Hormone receptor status:
• Estrogen receptor and/or progesterone receptor positive tumor by immunohistochemistry (IHC)

PATIENT CHARACTERISTICS:

• Pre- or post-menopausal
• ECOG performance status 0-1
• Life expectancy ≥ 6 months
• ANC ≥ 1,250/mm^3
• Platelet count ≥ 100,000/mm^3
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN (≤ 3 times ULN if liver metastasis is present)
• For patients with Gilbert syndrome, direct bilirubin will be measured instead of total bilirubin
• SGOT and SGPT ≤ 1.5 times ULN (≤ 3 times ULN if liver metastasis is present)
• Alkaline phosphatase ≤ 1.5 times ULN (≤ 3 times ULN if liver metastasis is present)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 3 months after completion of study therapy
• Able to swallow and retain oral medication
• Baseline QTc ≤ 450 msec
• No other invasive cancer within the past 5 years except for completely resected basal cell or squamous cell skin cancer or successfully treated cervical carcinoma in situ
• No malabsorption syndrome significantly affecting gastrointestinal function
• No diabetes, fasting glucose > 150mg/dL, or receiving ongoing anti-hyperglycemic therapies
• No concurrent uncontrolled illness including, but not limited to, any of the following:
• Ongoing or active infection requiring parenteral antibiotics
• Impaired lung function (i.e., COPD or lung conditions requiring oxygen therapy)
• Symptomatic congestive heart failure (NYHA class III or IV heart disease)
• Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within the past 6 months
• Uncontrolled hypertension, defined as systolic BP > 180 mm Hg or diastolic BP > 100 mm Hg on two consecutive measurements taken ≥ 1 week apart, despite adequate medical support
• Clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, or ventricular tachycardia that is symptomatic or requires treatment)
• Psychiatric illness and/or social situation that would compromise patient safety or limit compliance with study requirements, including maintenance of a compliance/pill diary

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy
• At least 2 weeks since prior investigational drugs
• No more than 4 prior chemotherapy treatments in the metastatic setting
• Does not include endocrine therapy or single-agent biologic therapy
• No concurrent CYP3A4 or CYP1A2 modifiers
• No other concurrent anticancer therapy, including chemotherapy, radiotherapy, surgery, immunotherapy, hormonal therapy, or biologic therapy
• Concurrent radiotherapy to painful bone metastases or areas of impeding bone fracture allowed provided radiotherapy is initiated before study therapy