Estrogen receptor positive breast cancer Cancer Malignant neoplasm of breast
Conditions
Interventions
Breast cancer patients are randomized based on menopausal status to Raloxifene or Tamoxifen or placebo, to Exemestane or Celecoxib or placebo.
Subjects with histologically-confirmed
Sponsors
European Institute of Oncology [Fondazione Istituto Europeo di Oncologia (FIEO)] (Italy)
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1. Female, aged at least 18 years old, no upper age limit 2. Performance status = 0 (SWOG) 3. Histologically-confirmed ER+ primary breast cancer candidated for conservative surgery 4. Stage T1-2, N0-1, M0 or women with larger tumors who refuse chemo and/or endocrine therapy before surgery 5. No previous treatment for breast cancer 6. Provision of written informed consent
Exclusion criteria
Exclusion criteria: 1. Previous treatment for breast cancer including chemotherapy and endocrine therapy 2. Patients eligible to neoadjuvant chemo and/or endocrine therapy 3. Evidence of previous superficial or deep venous thrombosis or other thrombo-embolic events of relevance (pulmonary embolism, stroke, etc) 4. Current anti-coagulant therapy 5. Moderate to severe alteration in hematologic profile, hemostasis, renal and hepatic metabolism 6. Clinically active peptic ulcer or gastroenteric disease 7. Severe retinal disease 8. Severe endometriosis (grade III-IV) or other proliferative disorders of the endometrium 9. Clinically active neurologic or psychiatric disease 10. Other medical contraindications as judged by the investigator 11. Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ 12. Pregnancy or current breast feeding (women of child-bearing potential must have a negative pregnancy test within 7 days before the start of study treatment)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is the change (tru-cut biopsy at baseline, and surgical specimen at surgery) in the percentage of neoplastic cells expressing the proliferation antigen Ki-67. Biopsy and surgical specimens are fixed in 10% neutral-buffered formalin for 6-8 hours before being embedded in paraffin. Sections (4-micron thick) are cut and stained with hematoxylin and eosin. Consecutive serial sections are used for immunohistochemical determinations. Expression Ki-67 will be determined by immunohistochemistry. Briefly, de-waxed tumor sections are pretreated with 3% hydrogen peroxide for 5 minutes to block endogenous peroxidase activity and then treated with a solution of 0.001 M EDTA (pH 8.0) at 99°C for 20 minutes to retrieve antigens. The tumor sections are then incubated with primary mouse monoclonal antibodies Ki-67 (clone Mib-1, 1:200 dilution). Primary endpoints will be detected at baseline and after 6 weeks of treatment (at biopsy and at surgery) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints: Change in ER and PgR expression and apoptosis as measured by Caspase-3. Change in markers of hemostasis and inflammation: fibrinogen, antithrombin III (AT III), plasminogen activator inhibitor-I (PAI-I), ultrasensitive C-reactive protein (US-CRP). Change in circulating hormones (estradiol, estrone, estrone-sulphate, and sex hormone binding globulin). DNA will be extracted from circulating lymphocytes and some genetic polymorphisms related to hormone and drug metabolism will be investigated. Expression of ER, PgR, Her2/neu, and Caspase-3 will be determined by immunohistochemistry. The tumor sections are then incubated with primary mouse monoclonal antibodies to ER (clone 1D5, 1:100 dilution), PgR (clone 1A6, 1:800 dilution), or with rabbit polyclonal antibody to the Her2/neu protein (1:3200 dilution), and to Caspase-3 (clone CPP32). Routine hematology and biochemistry assessments will be performed at the central laboratory of the institute. IGF-I levels will be determined from plasma by a chemiluminescent immunometric assay; antithrombin-III will determined by a kinetic colorimetric method. Serum concentration of US-CRP, SHBG and IGFBP-3 will be measured by a two-site chemiluminescent enzyme immunometric assay. Serum C-telopeptide and osteocalcin will be determined with a electrochemiluminescent immunometric assay. Serum estradiol and estrone-sulphate will be determined by the use of commercially available ultrasensitive radioimmunoassay kits. Genomic DNA will be extracted from frozen whole blood samples stabilized with EDTA by the use of a commercially available kit (QIAamp DNA Blood kit) purchased from Qiagen S.p.A, Milan, Italy).The evaluation of the CYP2D6 single nucleotide polymorphisms will be performed utilizing a semiautomated instrument (Light Cycler ? Roche) that allows more rapid assay procedures and guarantees a good product specificity. Specific primers and probes are | — |
Countries
Italy
Outcome results
None listed