Inclusion Criteria:

• Histologically proven, metastatic or locally advanced inoperable breast cancer
• Tumor considered potentially hormone-sensitive, i.e. presence by IHC of hormone receptors for estrogens (ER+ for more than 10% of cells) and/or progesterone (Pg+ for more than 10% of cells) or both. This expression may have been detected on the primary tumor or at a metastatic site. The method used will be reassessed by IHC if it involves a radioligand technique whenever it is possible to obtain histological material.
• Progressing on treatment with tamoxifen, given either as adjuvant treatment or for advanced/metastatic breast cancer. Any previous treatment with a steroidal or nonsteroidal antiaromatase in a neo-adjuvant, adjuvant or metastatic situation is permitted. Likewise, any previous treatment with chemotherapy and/or herceptin in a nonmetastatic situation is permitted.
• Post-menopausal patients
• Age > 18 years
• At least one measurable lesion according to the Response Evaluation Criteria for Solid Tumors (RECIST) criteria; for patients who only have bone metastases, an evaluable non-irradiated lytic lesion is required
• Performance Status (WHO): PS ≤ 2 (Appendix 1).
• Laboratory tests in accordance with the following criteria:

Neutrophils ≥ 2x109/l,Platelets ≥ 100x109/l,Hemoglobin ≥ 10 g/dl, ASAT, ALAT ≤ 2.5 N , or < 5 N when liver metastasis,bilirubin ≤ 1.5 N creatinin ≤ 1.5 N

• Signed, written consent before any study-related procedure

Exclusion Criteria:

• Men
• Pre-menopausal patients who are not receiving concurrent LHRH agonist therapy
• ER- and PR-negative patients
• Contraindication to antiestrogens (thromboembolic risk) or ZARNESTRA
• Non metastatic tumor susceptible to management by radiotherapeutic and/or surgical means
• T4d inflammatory tumor (PEV 2 or 3).
• Short-term, life-threatening lesions: hepatic invasion > 1/3 of liver volume, pulmonary lymphangitis, uncontrolled cerebral metastases, carcinomatous meningitis
• Sensory neuropathy > or = grade 1 (WHO)
• Previous history of uncontrolled cancers or controlled for less than 5 years, except basal cell skin cancers and in situ cancers of the cervix.
• Chronic diseases (somatic or psychiatric) with a poor prognosis
• subjects with enzyme-inducing anti-convulsants (e.g., phenytoin, phenobarbital, carbamazepine) : this treatment is not permitted while taking ZARNESTRA
• Patients who, for family, social, geographic or psychological reasons, could not be followed up correctly.