AUY922 With Lapatinib and Letrozole for ER+ HER2+ Advanced Breast Cancer

Inclusion Criteria:

- Age 18 years

- Able to sign Informed Consent

- Patients must have the following laboratory values:

Absolute Neutrophil Count (ANC) 1.5x109/L Hemoglobin (Hgb) 9 g/dl Platelets (plt)
100x109/L

- Potassium within normal limits

- Total calcium (corrected for serum albumin) and Phosphorus within normal limits

- Magnesium above LLN or correctable with supplements

- AST/SGOT and ALT/SGPT ≤ 1.5 x Upper Limit of Normal (ULN) if AP > 2.5 ULN

- AST/SGOT and ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN) if AP ≤ 5.0 x ULN if

- Serum bilirubin 1.5 x ULN

- Serum creatinin 1.5 x ULN or 24-hour clearance 50 ml/min

- Negative serum pregnancy test. The serum pregnancy test must be obtained prior to the
first administration of AUY922 (≤ 72 hours prior to dosing) in all pre-menopausal
women and women <2 years after the onset of menopause

- Histologically confirmed HER2 + and ER+ or PR + (i.e., HR+) Postmenopausal women with
Metastatic breast cancer or resistant locally advanced breast cancer.

- Stage of disease (stage IIIb/c not responding or progressing to standard therapy
with trastuzumab) or stage IV receiving first line treatment in the metastatic
setting . All patients should have documented clinical progression prior to entering
study

- Prior chemotherapy for metastatic stage IV disease is prohibited for patients
enrolled in phase II, but allowed up to 3 lines for patients enrolled in Phase I.
Prior neoadjuvant/adjuvant chemotherapy, antiestrogens, and radiotherapy are allowed.
Adjuvant hormonal therapy including aromatase inhibitors are permitted in the
adjuvant, neoadjuvant or metastatic setting if discontinued at least two weeks prior
to starting study treatment. Trastuzumab is permitted in the adjuvant, neoadjuvant or
metastatic setting if discontinued at least 4 weeks prior to study treatment

- Patients must have at least one measurable lesion as defined by RECIST. Irradiated
lesions and non-measurable disease are only evaluable for disease progression

- Patients must have tumors that carry HER-2 gene amplifications as determined by (i)
fluorescence in situ hybridization (FISH) or (ii) overexpression of HER-2 protein 3+
level assessed by immunohistochemistry. Patients who have previously been treated
with trastuzumab must be off treatment at least 6 weeks prior to starting study
treatment.

- World Health Organization (WHO) Performance Status of < 1

- Life expectancy of > 12 weeks

Exclusion Criteria:

- Unresolved diarrhea ≥ CTCAE (v4.02) grade 1

- Pregnant or lactating women

- Impaired cardiac function, including any one of the following:

- History (or family history) of long QT syndrome

- Mean QTc ≥ 450 msec on baseline ECG

- History of clinically manifested ischemic heart disease ≤ 6 months prior to study
start or History of heart failure or left ventricular (LV) dysfunction (LVEF ≤ 45%)
by MUGA or ECHO or arrythmia

- Patients known to be HIV positive. Testing is not required in the absence of clinical
signs and symptoms suggesting HIV infection.

- Known hypersensitivity to any of the study drugs or their excipients

- Participation in another clinical study within 30 days before first study treatment