Neoadjuvant Letrozole in Treating Postmenopausal Women With Estrogen-Receptor Positive and/or Progesterone-Receptor Positive Stage II, Stage IIIA, or Stage IIIB Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by reducing the production of estrogen. Giving letrozole before surgery may shrink the tumor so that it can be removed. PURPOSE: This phase II trial is studying how well neoadjuvant letrozole works in treating postmenopausal women who are undergoing surgery for estrogen-receptor positive or progesterone-receptor positive stage II, stage IIIA, or stage IIIB breast cancer.

Detailed Description
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OBJECTIVES: Primary Develop a predictive model of response (based on gene expression profiling) in postmenopausal women with estrogen- and/or progesterone-receptor positive stage II, IIIA, or IIIB breast cancer treated with neoadjuvant letrozole. Secondary Determine the response rate in patients treated with this drug. Determine changes in Ki67 proliferation rates in patients treated with this drug. Determine the rate of improvement in surgical outcomes in patients treated with this drug. Determine the long-term outcomes in patients treated with this drug. Determine the safety of this drug in these patients. Determine mechanisms of resistance to this drug in these patients. OUTLINE: This is a multicenter study. Patients receive neoadjuvant oral letrozole once daily for 16 weeks in the absence of disease progression. Patients then undergo breast surgery one day after the last dose of letrozole. Patients with partial response after 16 weeks may continue to receive letrozole for an additional 8 weeks before undergoing breast surgery. Patients are followed within 4 weeks after definitive surgery and then annually for 10 years. PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.

Official Title
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A Phase 2 Trial Of 4 Months Preoperative Letrozole 2.5 mg Daily For Postmenopausal Women With Estrogen Receptor Positive And/Or Progesterone Receptor Positive T2, T3, T4a-c, N0-2, M0 Breast Cancer- Novel Biomarkers for Aromatase Inhibitor Therapy

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: letrozole
* Procedure: conventional surgery


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed infiltrating adenocarcinoma of the breast by core needle biopsy Clinical stage T2-T4a-c, N0-2, M0 Palpable and measurable disease Previously untreated disease Benefits from neoadjuvant therapy that would improve surgical outcome AND meets criteria for 1 of the following: Marginal candidate for lumpectomy (e.g., lumpectomy feasible but patient at risk for positive margins or poor cosmetic outcome) AND patient desires breast-conserving surgery Ineligible for lumpectomy due to size of primary tumor, but modified radical mastectomy feasible AND patient desires breast-conserving surgery Inoperable disease AND systemic therapy required for disease to become operable by modified radical mastectomy Bilateral primary tumors allowed provided both tumors are consistent with entry criteria No inflammatory carcinoma (defined as peau d' orange affecting at least one third of the breast) Direct extension of the tumor to the skin allowed No metastatic breast disease, except isolated ipsilateral supraclavicular lymphadenopathy Hormone receptor status: Estrogen- and/or progesterone-receptor positive disease based on 10% or more nuclear staining of the invasive component of the tumor PATIENT CHARACTERISTICS: Age Postmenopausal Sex Female Menopausal status Postmenopausal, defined as meeting 1 of the following criteria: Cessation of menstrual periods for at least 1 year Bilateral surgical oophorectomy Follicle-stimulating hormone and estradiol levels in the postmenopausal range Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Not specified Hepatic No severe liver dysfunction that would preclude study participation Renal Not specified Other Willing and able to provide biopsy material Willing to undergo breast surgery after neoadjuvant treatment No condition (e.g., confusion, infirmity, or alcoholism) that would preclude study compliance No other concurrent active and progressive invasive malignancies No other concurrent severe disease that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent immunotherapy or biological response modifiers for breast cancer Chemotherapy No prior chemotherapy for breast cancer No concurrent chemotherapy for breast cancer Endocrine therapy At least 2 weeks since prior hormone replacement therapy or phytoestrogenic herbal, alternative, or over-the-counter (OTC) sex hormone remedies No prior hormonal agents for breast cancer No prior aromatase inhibitors, tamoxifen, raloxifene, or other antiestrogen or selective estrogen receptor modulators No concurrent drugs known to affect sex hormone status, including hormone replacement therapy or phytoestrogenic herbal, alternative, or OTC remedies No other concurrent endocrine therapy for breast cancer Radiotherapy No prior radiotherapy for breast cancer No concurrent radiotherapy for breast cancer Surgery Prior sentinel node biopsy allowed No other concurrent surgery for breast cancer Other More than 30 days since prior non-approved or experimental drugs Concurrent bisphosphonates for osteoporosis allowed No other concurrent treatment for breast cancer

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: Treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Letrozole/Surgery<br> | Drug: letrozole<br> <br> Procedure: conventional surgery<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Predictive model for response as assessed by gene expression profiling |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  |  | 
| Changes in Ki67 proliferation rates |  |  | 
| Rate of improvement in surgical outcomes |  |  | 
| Long-term outcomes |  |  | 
| Safety |  |  | 
| Mechanisms of resistance |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer