Efficacy of Anastrozole and Fulvestrant in Patients With ER Positive, HER2 Negative, Operable 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 anastrozole or fulvestrant may fight breast cancer by lowering the amount of estrogen the body makes or by blocking the use of estrogen by the tumor cells. Giving hormone therapy before surgery may be an effective treatment for breast cancer. It is not yet known whether anastrozole is more effective than fulvestrant when given before surgery in treating women with breast cancer. PURPOSE: This randomized phase II trial is studying anastrozole to see how well it works compared with fulvestrant in treating postmenopausal women with stage II or stage III breast cancer that can be removed by surgery.

Detailed Description
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OBJECTIVES: Primary To compare the clinical response rates (complete and partial responses) at 6 months in postmenopausal women with operable stage II or III breast cancer treated with neoadjuvant anastrozole vs fulvestrant. Secondary To compare the breast surgery conservation rate in patients treated with these drugs. To correlate imaging findings by mammography, ultrasonography, and MRI with histological and clinical response in these patients and with sensitivity profile to these drugs. To compare histological response in patients treated with these drugs. To define criteria appropriate for neoadjuvant hormonal therapy. To correlate baseline molecular characteristics and modifications during treatment with response in these patients. To compare the tolerability of these drugs in these patients. To compare the serum proteomic profile of patients treated with these drugs. To correlate 3-year event-free and overall survival rates with clinical and histological response in these patients. OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral anastrozole once daily for 4-6 months in the absence of clinical progression. Arm II: Patients receive fulvestrant intramuscularly on days 1, 15, and 29 in the first month and then every 28 days in each subsequent month. Treatment continues for 4-6 months in the absence of clinical progression. Patients in both arms then undergo surgery and radiotherapy according to institutional guidelines. Patients then receive adjuvant hormonal therapy for at least 5 years. After completion of study therapy, patients are followed periodically for up to 3 years.

Official Title
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A Randomized Multicenter Phase II Study Identifying Hormone Sensitivity Profiles and Evaluating the Efficacy of Anastrozole and Fulvestrant in the Neo-adjuvant Treatment of Operable Breast Cancer in Postmenopausal Women.

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: anastrozole
* Drug: fulvestrant


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed infiltrating breast adenocarcinoma Large, operable tumor Stage T2 (≥ 3 cm) or T3-T4 (excluding inflammatory disease), N0-N3, M0 disease No bilateral inflammatory breast tumors (T4d [PEV-2 or PEV-3]) Elston-Ellis grade I or II and mitotic index 1 or 2 (if < 65 years of age) At least 1 embedded and 1 frozen biopsy sample available No multifocal or multicentric tumors for which breast conservation cannot be envisaged No ErbB2-overexpressing tumors (HER2 3+ by IHC OR HER2 2+ by IHC and FISH positive) Hormone receptor status: Estrogen receptor and/or progesterone receptor positive tumor (> 10%) as assessed by IHC PATIENT CHARACTERISTICS: Female Postmenopausal ECOG performance status 0-2 ANC ≥ 2,000/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 10 g/dL Creatinine ≤ 1.5 times upper limit of normal (ULN) Total bilirubin ≤ 1.25 times ULN AST and ALT ≤ 1.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN No other cancer within the past 10 years, except basal cell skin cancer or previously treated carcinoma in situ of the cervix No uncontrolled cardiac pathology, including any of the following: Angina pectoris Congestive cardiac insufficiency Myocardial infarction within the past 3 months No known history of hemorrhagic diathesis No known allergy to the study drugs or their excipients No congenital galactosemia, glucose malabsorption syndrome, or lactase deficiency No chronic somatic or psychiatric illness with pejorative prognosis No geographical, social, or psychiatric condition that would preclude study compliance and follow-up schedule No individual deprived of liberty or placed under the authority of a tutor PRIOR CONCURRENT THERAPY: No prior chemotherapy, hormonal therapy, or any targeted treatment for the breast tumor At least 2 weeks since prior hormone replacement therapy for menopause No concurrent long-term anticoagulation treatment No concurrent participation on another therapeutic trial involving an experimental molecule
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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Anastrozole | Drug: anastrozole<br>* 1 mg/day for either 4 months or 6 months depending on the clinical evaluation<br>|
| Experimental: Arm B<br>Fulvestrant | Drug: fulvestrant<br>* 500mg at day 1, day 15 and day 29 500mg every 28 days for either 4 months or 6 months depending on the clinical evaluation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical tumor response as assessed by RECIST criteria |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Breast surgery conservation rate |  | Post surgery | 
| Histological tumor response as assessed by the Sataloff scale |  | Post surgery | 
| Tumor response as assessed by mammography, ultrasonography (RECIST criteria), and MRI |  | at baseline, after the first month of treatment, and then before surgery | 
| Biological prognosis and predictive response factors |  | 3 years | 
| Relapse-free survival rate |  | 3 years | 
| Event-free survival rate |  | 3 years | 
| Overall survival rate |  | 3 years | 
| Toxicity as assessed by NCI CTCAE v3.0 |  | During neoadjuvant treatment | 

 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, stage IIIC breast cancer