A Randomized, Open-label, Multicenter, Phase II Study Comparing the Effects on Proliferation and the Efficacy and Tolerability of Fulvestrant (FASLODEX™) 500 mg with Fulvestrant (FASLODEX™) 250 mg when given as Neoadjuvant Treatment in Postmenopausal Women with Estrogen Receptor Positive Breast Cancer (T2, 3, 4b, N0-3, M0) - NEWEST – Neoadjuvant Endocrine therapy for Women with Estrogen Sensitive Tumors

Conditions: Postmenopausal Women with Estrogen Receptor Positive Breast Cancer (T2, 3, 4b, N0-3, M0)

Registration Number: EUCTR2004-003617-16-AT

Lead Sponsor: AstraZeneca Österreich GmbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 160

Inclusion Criteria

1. Provision of written informed consent.
2. Histologically/cytologically confirmed invasive breast cancer, ER positive as defined by the local laboratory
3. Operable or potentially operable locally advanced tumor (T2, 3, 4b, N0-3, M0). The largest diameter of the tumor as measured by ultrasound or by MRI must be ³ 2 cm. Patients with two measurable nodules will be eligible as long as both lesions are biopsied and have similar histology and are both ER positive.
4. Postmenopausal woman, defined as a woman fulfilling any 1 of the following criteria:
· Age ³ 60 years
· Age ³ 45 years with amenorrhea ³ 12 months with an intact uterus
· Having undergone a bilateral oophorectomy
· FSH and estradiol levels in postmenopausal range (utilizing ranges from the testing laboratory facility).
5. Willingness to undergo biopsy at baseline and at 4 weeks and surgery at 16 weeks
6. WHO performance status 0, 1 or 2
For inclusion in the genetic component of the study, patients must fulfill the following criteria:
1. Provision of informed consent for genetic sampling and analyses
If a patient declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this Clinical Study Protocol, so long as they consent.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Inoperable due to satellite skin nodules or true inflammatory carcinoma.
2. Multifocal disease (> 2 major tumor nodules). Patients with more than one primary tumor will be excluded.
3. Presence of metastatic disease as defined by the American Joint Committee on Cancer (AJCC) guidelines revised in 2002 (Singletary, 2002). Metastatic evaluation should be performed according to the usual guidelines of the institutions. It is recommended that the following evaluations should be done:
· Chest X-ray
· Liver function tests
· CBC with differential cell count and platelet count.
· Abdominal CT scan if liver function tests significantly elevated
· CT scan of the chest and abdomen for clinical stage ³ T3, or > N1
· Bone scan if bony discomfort, elevated serum alkaline phosphatase, ³ T3 or >N1 clinical disease
· Bilateral mammograms
4. Any previous treatment for breast cancer
5. Unwillingness to stop taking any drug known to affect sex hormonal status (including HRT), or a patient in whom it would be inappropriate to stop
6. Current or prior malignancy within previous 3 years (other than adequately treated basal cell or squamous cell carcinoma of the skin, in-situ carcinoma of the cervix)
7. Any of the following laboratory values:
· Platelets < 100 ´ 109 / L
· Total bilirubin > 1.5 ´ ULRR
· ALT or AST > 2.5 ´ ULRR
8. Any severe concurrent condition that would preclude surgery or that would jeopardize compliance with the protocol, eg, uncontrolled cardiac disease or uncontrolled diabetes mellitus
9. Patients known to be HIV, hepatitis B or C positive are not eligible because of the potential to confound the study endpoints, although patients will not be routinely screened for HIV, hepatitis B or C
10. History of :
· bleeding diathesis (ie, disseminated intravascular coagulation [DIC], clotting factor deficiency) or
· long-term anticoagulant therapy (other than antiplatelet therapy and low dose warfarin – see Section 3.7)
11. History of hypersensitivity to castor oil
12. Treatment with a non-approved or experimental drug within 4 weeks before randomization