RATIONALE: Drugs used in chemotherapy, such as doxorubicin and paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving chemotherapy before and after surgery may shrink the tumor so it can be removed and may kill any tumor cells remaining after surgery.

PURPOSE: This randomized phase II trial is comparing two different regimens of doxorubicin and paclitaxel to see how well they work in treating women who are undergoing surgery for breast cancer.

Condition	Treatment or Intervention	Phase
stage II breast cancer stage IIIA breast cancer stage IIIB breast cancer stage IIIC breast cancer	Drug: doxorubicin  Drug: paclitaxel  Procedure: adjuvant therapy  Procedure: biological markers  Procedure: biopsies  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: cytogenetic analysis  Procedure: diagnostic test  Procedure: gene expression profiling  Procedure: magnetic resonance imaging  Procedure: mammography  Procedure: neoadjuvant therapy  Procedure: surgery  Procedure: ultrasonography	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine whether tumors in women with palpable invasive breast cancer with wild type p53 are more sensitive to doxorubicin than to paclitaxel when given as sequential single-agent neoadjuvant chemotherapy.
• Determine whether tumors with inactivated p53 are more sensitive to paclitaxel than to doxorubicin when given as sequential single-agent neoadjuvant chemotherapy in these patients.

Secondary

• Correlate other biological markers (physiological and molecular) with tumor response in patients treated with these regimens.
• Determine changes in these biological markers during and after neoadjuvant chemotherapy in these patients.
• Compare breast MRI, in terms of assessing tumor response, with physical exam, mammogram, and ultrasound in patients treated with these regimens.
• Determine whether there are MRI indicators (e.g., tumor morphology or lesion enhancement) that are predictive of response in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor size (> 5 cm vs ≤ 3-5 cm) and presence of palpable regional lymph nodes (yes vs no). Patients are randomized to 1 of 2 treatment arms.

All patients undergo biopsy, bilateral mammogram, MRI, ultrasound, blood marker, molecular (gene microarrays and functional p53 status), and physiologic studies before initiation of neoadjuvant chemotherapy. Some of these studies are repeated after completion of treatment with the first chemotherapeutic agent and after completion of treatment with the second chemotherapeutic agent as outlined below.

• Patients receive doxorubicin IV on days 1, 15, 29, and 43. Patients with no residual tumor (indicated by clinical evaluation and radiologic studies) after completion of doxorubicin undergo definitive surgery. After surgery, patients receive paclitaxel IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, and 57. Patients with residual tumor > 2 cm after completion of doxorubicin undergo 8-12 core needle biopsies. Patients with residual tumor < 2 cm after completion of doxorubicin undergo 4-6 core needle biopsies. After core needle biopsies, patients receive paclitaxel as above.
• Patients receive paclitaxel IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, and 57. Patients with no residual tumor (indicated by clinical evaluation and radiologic studies) after completion of paclitaxel undergo definitive surgery. After surgery, patients receive doxorubicin IV on days 1, 15, 29, and 43. Patients with residual tumor > 2 cm after completion of paclitaxel undergo 8-12 core needle biopsies. Patients with residual tumor < 2 cm after completion of paclitaxel undergo 4-6 core needle biopsies. After core needle biopsies, patients receive doxorubicin as above.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Samples from core needle biopsies are analyzed by microarray analysis for gene expression profiles.

Patients are followed every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study within 4-5 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of invasive breast cancer
• Tumor ≥ 3 cm and palpable
• Multiple masses are allowed provided at least 1 mass is ≥ 3 cm
• Clinically positive axillary or supraclavicular lymph nodes allowed
• Fine needle aspiration or core needle biopsy positive for invasive breast cancer AND/OR fine needle aspiration of lymph nodes positive
• HER2/neu-positive OR negative
• No inflammatory breast cancer
• No distant metastases
• Hormone receptor status:
• Estrogen receptor (ER)-positive OR ER-negative

PATIENT CHARACTERISTICS: Age

• 18 and over

Sex

• Female

Menopausal status

• Premenopausal or postmenopausal

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count ≥ 1,000/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 2 times upper limit of normal (ULN)
• SGOT ≤ 2 times ULN

Renal

• Not specified

Cardiovascular

• LVEF ≥ 50%
• No congestive heart failure
• No serious conduction system abnormality
• No other significant cardiovascular disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Patients with other prior or concurrent malignancies allowed provided they have received no prior chemotherapy AND they are likely to have been cured from a prior malignancy
• No severe medical or psychiatric condition that would preclude study compliance
• No known HIV positivity

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• No prior hormonal therapy for breast cancer

Radiotherapy

• No prior radiotherapy for this malignancy

Surgery

• Not specified

Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
      Massachusetts General Hospital Cancer Center, Boston,  Massachusetts,  02114-2617,  United States

Study chairs or principal investigators

Alphonse G. Taghian, MD, PhD,  Principal Investigator,  Dana-Farber/Harvard Cancer Center   

Study ID Numbers:  CDR0000382123; DFCI-99278; NCT00096291
Record last reviewed:  March 2005
Last Updated:  March 22, 2005
Record first received:  November 9, 2004
ClinicalTrials.gov Identifier:  NCT00096291
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08