Letrozole or Tamoxifen Citrate in Treating Older Postmenopausal Women Undergoing Surgery for Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by blocking the uptake of estrogen. Tamoxifen citrate may fight breast cancer by blocking the use of estrogen by the tumor cells. It is not yet known whether letrozole or tamoxifen citrate is more effective when given before surgery in treating older women with breast cancer. PURPOSE: This randomized phase III trial is studying letrozole to see how well it works compared with tamoxifen citrate in treating older postmenopausal women undergoing surgery for breast cancer.

Detailed Description
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OBJECTIVES: Primary Investigate the changes in Ki67 and PCNA in postmenopausal women with estrogen receptor-positive (ER+) breast cancer after 4 months of treatment with letrozole vs tamoxifen citrate. Secondary Compare the response after 4 months of therapy. Define the resistant forms of cancer in patients treated with these regimens. Define the molecular signature predictive of sensitivity or resistance to ER+ breast adenocarcinoma by gene and serum protein profiling. Search for serum protein profiles predictive of recurrence-free interval. OUTLINE: Patients are randomized into 1 of 2 intervention arms. Arm I: Patients receive oral letrozole once daily for 16 weeks. Arm II: Patients receive oral tamoxifen citrate once daily for 16 weeks. Patients in both arms then undergo surgery. Blood and tumor tissue samples are collected at baseline and after completion of neoadjuvant therapy for changes in Ki67 and PCNA and serum protein profiling analysis. After completion of study therapy, patients are followed up every 6 months for 3 years, and then once a year for 5 years.

Official Title
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Randomized Double-blind Study to Compare Two Neo-adjuvant Treatments: an Anti-aromatase vs SERM for Postmenopausal Women With ER+ Breast Adenocarcinoma: Effect on Intermediate Predictive Biological Response to Treatment.

Conditions
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Breast Cancer

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed invasive breast adenocarcinoma Clinically T2 tumor and/or > 1 cm by echography Estrogen receptor (ER)-positive and > 10% of the tumor cells positive No ER-negative disease No prior breast cancer No metastatic or inflammatory breast adenocarcinoma PATIENT CHARACTERISTICS: Postmenopausal No cardiac function that could contraindicate surgery or medical treatment (e.g., radiotherapy and/or chemotherapy) No prior malignancies within the past 5 years except for nonmelanoma skin cancer or carcinoma in situ of the cervix No mental incapacitation that would preclude consent No contraindication to tamoxifen citrate or letrozole PRIOR CONCURRENT THERAPY: More than 8 days since prior hormone-replacement therapy or other treatment (i.e., phytoestrogen) for menopause No concurrent therapy that would modify the expression of the genes regulated by estrogen No concurrent participation in another clinical study

Ages Eligible for Study
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Minimum Age: 65 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
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral letrozole once daily for 16 weeks. | Drug: letrozole<br>* Given orally<br>|
| Experimental: Arm II<br>Patients receive oral tamoxifen citrate once daily for 16 weeks. | Drug: tamoxifen citrate<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Ki67 and PCNA after 4 months of treatment with letrozole vs tamoxifen citrate |  | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Molecular signature predictive of sensitivity or resistance to estrogen receptor-positive breast adenocarcinoma |  | up to 24 months | 
| Survival rate |  | up to 24 months | 

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