Phase III Study of Atamestane Plus Toremifene Versus Letrozole in Advanced Breast Cancer

Inclusion Criteria: * Women age 18 years or older * Pathological or histological confirmation of breast cancer at initial diagnosis or at the time of metastases * ECOG performance status of 0, 1 or 2 or Karnofsky performance status of 60 or higher * Predicted life expectancy of 12 weeks or more * Postmenopausal endocrine status. LH/FSH levels in the postmenopausal range in women whose menopause occurred less than 5 years ago * Locally recurrent, locally advanced, locally metastatic disease not amenable to radiation therapy or surgery and/or distant metastatic disease * At least one tumor localization measurable in 2 dimensions (one diameter at least 2 cm for soft tissue/visceral disease assessed by CT/MRI scan or conventional X-ray technique, one diameter at least 1 cm for bone lesions assessed by conventional X-ray techniques) * Estrogen receptor and/or progesterone receptor positive (by laboratory/institutional standard) at the time of initial diagnosis or determined during subsequent biopsy/surgery of metastases * Written informed consent obtained Exclusion Criteria: * Prior hormonal therapy to treat locally recurrent, locally advanced or metastatic disease * Prior adjuvant therapy with aromatase inhibitors or antiestrogens/SERMs within 12 months prior to enrollment * Progression of disease during therapy with antiestrogens (including SERMs administered for prevention of osteoporosis) * Life-threatening locally recurrent, locally advanced or metastatic disease or disease requiring chemotherapeutic intervention (such as inflammatory breast cancer) * History of known CNS metastases, significant neurological dysfunction including active seizures, or clinical signs of other significant neurological diseases * Other active malignancy (except basal cell carcinoma of the skin or in situ cervical cancer). Patients with previous malignancies must be without evidence of disease for at least five years * Renal insufficiency (serum creatinine \> 2.0 mg/dL) * Aspartate aminotransferase, alanine aminotransferase or serum bilirubin levels more than 2.5 times upper limit of normal * Hemoglobin \<9 g/dL * Platelet count of less than 100,000 platelets per mm3 * Total white blood cell count of less than 2,000 cells per mm3 * Premenopausal endocrine status; pregnant or lactating females * Usage of an investigational drug within the thirty (30) days prior to enrollment; or the planned usage of an investigational drug other than the study medication during the course of the current study * Contraindication to use of toremifene, atamestane, letrozole or any of the inactive components of their formulations * Prior enrollment in this study