Epirubicin in Treating Women Who Are Undergoing Surgery for Stage I, Stage II, or Stage III Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as epirubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving epirubicin before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II trial is studying how well epirubicin works in treating women who are undergoing surgery for stage I, stage II, or stage III breast cancer.

Detailed Description
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OBJECTIVES: Primary Determine the complete pathological and clinical response rate in women undergoing surgery for resectable stage I-III breast cancer treated with neoadjuvant dose-intensified epirubicin hydrochloride. Secondary Determine the toxicity of this regimen in these patients. Determine the predictive value of HER2 gene amplification and topoisomerase II-alpha gene amplification or deletion for disease progression and pathological and clinical complete response in patients treated with this regimen. Correlate gene expression profiles with pathologic complete response, clinical complete response, less than complete response, and disease progression in patients treated with this regimen. OUTLINE: Patients receive epirubicin hydrochloride IV on day 1 and pegfilgrastim subcutaneously on day 2. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Four weeks later, patients undergo partial mastectomy or simple mastectomy plus an axillary staging procedure. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Official Title
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Prediction of Response or Resistance to Dose Intensified Pre-Operative Epirubicin Therapy of Operable Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: pegfilgrastim
* Drug: epirubicin hydrochloride
* Procedure: conventional surgery


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed invasive breast cancer Stage I, II, or III disease (T1, T2, or T4; N0-2; M0) Resectable disease Unidimensionally measurable disease Primary tumor ≥ 2 cm No known distant metastases Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Sex Female Menopausal status Not specified Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic WBC ≥ 3,500/mm^3 Hemoglobin ≥ 8 g/dL Platelet count ≥ 100,000/mm^3 No known untreated bleeding diathesis Hepatic AST ≤ 2 times upper limits of normal Bilirubin ≤ 1.5 mg/dL Renal Creatinine ≤ 1.5 mg/dL OR Creatinine clearance ≥ 60 mL/min Cardiovascular LVEF ≥ 50% on echocardiogram, MUGA, or cardiac catheterization Other Not pregnant or breastfeeding Fertile patients must use effective contraception Negative pregnancy test No concurrent illness that would preclude study treatment No known hypersensitivity to Escherichia coli-derived proteins, pegfilgrastim, filgrastim (G-CSF), or any other component of these products PRIOR CONCURRENT THERAPY: Not specified

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epirubicin<br> | Biological: pegfilgrastim<br>* 6 mg in a syringe<br>* Other names: Neulasta;Drug: epirubicin hydrochloride<br>* 120 MG q 2 weeks for 4 cycles<br>Procedure: conventional surgery<br>* to remove small piece of cancer<br>* Other names: Biopsy will involve a small surgical incision to remove a piece of the cancer.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete pathological response rate by tumor analysis after surgery | No evidence of microscopic invasive tumor at the primary tumor site in the surgical specimen. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete clinical response rate by diagnostic mammogram at baseline and at 8 weeks | Bilateral (if both breasts are present) Mammograms (within 4 weeks of study entry) | 4 weeks | 
| Toxicity by physical exam and medical history every 14 days prior to surgery | A physical exam Physical examination with recording of tumor size, if palpable. | 2-4 weeks | 
| Predictive value of HER2 gene amplification and topoisomerase II-alpha gene amplification or deletions for pathologic complete response, clinical complete response or disease progression after surgery | Patients whose tumors are positive for estrogen receptor (>1% staining by immunohistochemistry) or progesterone receptor (institutional definition) should receive post-operative hormonal therapy for 5 years. | 5 years | 
| Gene expression after surgery | Patients whose tumors are positive for estrogen receptor (>1% staining by immunohistochemistry) or progesterone receptor (institutional definition) should receive post-operative hormonal therapy for 5 years. | 5 years | 

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