This is a pivotal phase II, multicenter, open-label trial, designed to compare the efficacy of exemestane versus anastrozole as a first line treatment for advanced breast cancer. One hundred postmenopausal patients, with metastatic, positive hormone receptor breast cancer will be enrolled in this trial.

The primary study endpoint is objective response rate. The study has been designed following Simon's test, with a p1-p0=0.15. p1 is the optimum level of activity of the experimental treatment (exemestane), and p0 is the minimum expected activity. In this study, p1 is 25% (25% of RR) and p0 is 10% (10% of RR). With an alpha error of 0.05 and a beta error of 0.1, Simon test establishes a first step of 21 patients per treatment arm. If at least 2 objective responses are observed in exemestane arm, recruitment will continue until 100 patients have been recruited. After this second recruitment phase, at least 7 objective responses must be observed to confirm the expected exemestane level of activity.

Inclusion Criteria:

• Pathological diagnoses of breast cancer.

• Postmenopausal women, defined as:

  • Bilateral surgical oophorectomy or amenorrhoea >= 5 years;
  • Age >= 56 years old and amenorrhoea >= 1 year;
  • Chemotherapy induced amenorrhoea >= 2 years;
  • Radiotherapy induced amenorrhoea at least 3 months before:
  • Age < 56 and < 5 years of amenorrhoea: follicle-stimulating hormone (FSH) levels to confirm postmenopausal status.

• Metastatic breast cancer (stage IV) or non-operable locally advanced breast cancer (stage IIIB).

• Positive estrogen and/or progesterone receptors as >10% cells or >10fmol/mg.

• Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

• Patients who have received adjuvant tamoxifen are eligible, if progression has been established at least 24 months since treatment start.

• Neoadjuvant chemotherapy is allowed if progression has been established at least 12 months after end of treatment.

• Patients may have received a first line of chemotherapy for advanced disease, but treatment must have ended at least 4 weeks before enrolment, and all acute toxicities must be resolved. Previous treatment with Herceptin is allowed.

• Normal haematological, hepatic and renal functions.

• Performance status ECOG of 0, 1, 2.

• Life expectancy superior to 3 months.

• Written informed consent.

Exclusion Criteria:

• Previous hormone treatment for metastatic disease.
• Previous treatment with aromatase inhibitors.
• Inflammatory breast cancer, or aggressive metastatic disease, or visceral lesions, or metastasis in the central nervous system (CNS).
• Non-measurable disease.
• Second malignancy except for basal skin carcinoma or cervical in situ carcinoma adequately treated. If other malignancies, patient must have a disease-free period superior to 5 years.
• Treatment with any investigational product in the 4 previous weeks.
• Patients with negative estrogen and progesterone receptor tumours.