Letrozole, Anastrozole, Exemestane, or Tamoxifen Citrate in Treating Postmenopausal Women With Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Estrogen can cause the growth of breast cancer cells. Aromatase inhibitors, such as letrozole, anastrozole, and exemestane, may fight breast cancer by lowering the amount of estrogen the body makes. Hormone therapy, using tamoxifen citrate, may fight breast cancer by blocking the use of estrogen by the tumor cells. It is not yet known whether aromatase inhibitors or tamoxifen citrate have less effect on memory in patients receiving treatment for breast cancer. PURPOSE: This randomized phase III trial is studying letrozole, anastrozole, or exemestane to see how they effect memory compared with tamoxifen citrate in treating postmenopausal women with breast cancer.

Detailed Description
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OBJECTIVES: Primary To evaluate verbal episodic memory in patients with breast cancer after 6 months of treatment with aromatase inhibitors (AI) vs tamoxifen citrate. Secondary To evaluate cognitive functions of these patients at month 6 and 12 of treatment. To evaluate the psychological and social impact on these patients at month 6 and 12 of treatment. OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral tamoxifen citrate once daily for 1 year in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive an oral aromatase inhibitor (letrozole, anastrozole, or exemestane) once daily for 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo cognitive, psychological, social, and quality of life assessments every 6 months using the CDS scale, the Edinburgh Handedness Inventory, the Mini Mental Test, the French version of the National Adult Reading Test, the Benton Visual Retention test, the direct and indirect capacities of the WAIS-R, the WMS sequential visual-spatial capacity, the dual task test, categorical and formal verbal fluency, the Trail making test, the Stroop test, the Wisconsin Card Sorting test, the choice reaction time test, the sequential visual spatial capacity, the HADS scale, IADL, and QLQ-C30 questionnaires. After completion of study treatment, patients are followed for 1 year.

Official Title
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A Prospective, Randomized, Open-label, Multicenter Study Evaluating the Effects on Cognitive Functions of Adjuvant Endocrine Therapy in Postmenopausal Women With Breast Cancer.

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: anastrozole
* Drug: exemestane
* Drug: letrozole
* Drug: tamoxifen citrate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed breast cancer No metastatic disease Meets criteria for initiating adjuvant endocrine therapy Hormone receptor status: Estrogen receptor- and/or progesterone receptor-positive disease PATIENT CHARACTERISTICS: Postmenopausal, defined as no menstruation for ≥ 1 year, confirmed by a measurement of FSH and 17-beta-estradiol Karnofsky performance status 80-100% Native speaker of French Beneficiary of a French Social Security insurance plan No prior cognitive disorders No depression or other confirmed active psychiatric disease Able to undergo the medical monitoring of the trial due to geographic, social or psychological reasons No personal or family history of thromboembolic disease PRIOR CONCURRENT THERAPY: No prior adjuvant chemotherapy No concurrent follow-up participation on another study No concurrent treatment with psychotropic substances (i.e., long half life benzodiazepines, antipsychotics, anticholinesterase)

Ages Eligible for Study
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Maximum Age: 70 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: Treatment
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral tamoxifen citrate once daily for 1 year in the absence of disease progression or unacceptable toxicity. | Drug: tamoxifen citrate<br>* Given orally<br>|
| Experimental: Arm II<br>Patients receive an oral aromatase inhibitor (letrozole, anastrozole, or exemestane) once daily for 1 year in the absence of disease progression or unacceptable toxicity. | Drug: anastrozole<br>* Given orally<br>Drug: exemestane<br>* Given orally<br>Drug: letrozole<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in verbal episodic memory performance after 6 months of treatment, using the Rey Auditory Verbal Learning Test |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in other cognitive functions at 6 and 12 months of treatment |  |  | 
| Psychological and social impact at 6 and 12 months of treatment, using the HADS scale and quality of life questionnaires (i.e., IADL and QLQ-C30) |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IA breast cancer, stage IB breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, estrogen receptor-positive breast cancer, progesterone receptor-positive breast cancer