Biological Response to Tamoxifen (TAM) in Patients With Breast Cancer Non Metastatic RH+

Study Overview
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Brief Summary
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The biological response to treatment with tamoxifen in the preoperative situation is studying in this protocol. This study will enrolls patients with non-metastatic breast cancer HR +. The relationship between the CYP2D6 polymorphism, pharmacokinetics and biological efficacy of TAM will be studied.

Official Title
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Phase II Study Evaluating According to the Polymorphism of CYP2D6, the Rate of Biological Response to Treatment With Tamoxifen (TAM) Administered in Pre-operative Situation in Patients With Breast Cancer Non Metastatic HR+

Conditions
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Non Metastatic Breast Cancer

Intervention / Treatment
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* Drug: tamoxifen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult Females (≥ 18 years), with effective contraception. The contraceptive should not use estrogen to a derivative. It must be continued during treatment with tamoxifen for at least two months after his arrest. Histologically confirmed diagnosis of invasive breast cancer, previously untreated. Patients have been supported for a breast cancer may be included if a period of at least 2 years between the last systemic treatment of inclusion in the study. Primary tumor hormonopositive: ER and / or PR ≥ 50% by immunohistochemistry. Lack of HER2 overexpression Palpable primary tumor or greater than or equal to 20 mm in diameter, measured by ultrasound Patient scheduled to undergo breast cancer surgery No metastases Clinical Stage M0 Performance index ≤ 1 (OMS) Neutrophils WBC > or = 1500 / mm3, Platelets > or = 100 000/mm3 Hemoglobin ≥10 g/dL Normal liver function: bilirubin ≤ 1.5 x ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases). Normal renal function (creatinine ≤ 1.5 mg / dL or creatinine clearance ≥ 60 mL / min) Cardiac function (MUGA scan or ultrasound February> 55%) and lung function, 5.2.2 Criteria related to participation in the study: Patient affiliated to social security, Patient has signed and dated consent Non-Inclusion Criteria: Pregnant or Breastfeeding women Use of St. John's Wort (herbal tea ...) within 5 days before starting treatment Consumption of grapefruit juice in the last 5 days of starting treatment Congenital galactosemia Glucose and galactose malabsorption Lactase deficiency Co-medications that may interfere with cytochrome P450: Ongoing Enzyme inducers: Antiepileptic drugs: carbamazepine, phenobarbital, phenytoin Antinfectieux: rifampin, rifabutin, névrirapine, griséofilvine, efavirenz Ongoing Enzyme Inhibitors: Inhibitors of serotonin reuptake: fluoxetine, paroxetine Thioridazine. Quinidine Amiodarone Ca antagonists: diltiazem, verapamil azole antifungals ketoconazole, fluconazole, miconazole. No protease inhibitors: ritonavir, nelfinavir, amprenavir, indinavir. Macrolides: erythromycin, clarithromycin, josamycin

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tamoxifene<br> | Drug: tamoxifen<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the response to Tamoxifen treatment, in preoperative situations (immediately operable patients) in patients with positive Hormone Receptors (HR+) non-metastatic breast cancer | The primary endpoint is the determination of the variation in the KI-67 expression, a marker of cell proliferation, at the tumour level between the initial biopsy (T0) and after 5 weeks of tamoxifen treatment, in relation to cytochrome 2D6 polymorphisms. A 50% geometric reduction in KI-67 expression at 5 to 7 weeks should be considered as a major response | 5 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tamoxifen,, Breat Cancer, Pharmacogenetic, non metastatic breast cancer, HR +