Paclitaxel and Radiation Therapy in Treating Patients Undergoing Surgery for Stage II or Stage III Breast Cancer

OBJECTIVES:

Primary

• Evaluate the efficacy of paclitaxel and concurrent radiotherapy (as measured by pathologic response rates) in patients with stage II or III breast cancer.

Secondary

• Evaluate the toxicities of this treatment regimen.
• Correlate paclitaxel-induced tumor response with local recurrence-free survival, distant disease-free survival, and overall survival.
• Evaluate protein expression profiles by mass spectrometry in biopsy material and blood specimens collected before and after treatment with paclitaxel.

OUTLINE:

• Neoadjuvant chemotherapy: Patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
• Chemoradiotherapy: Beginning 3-4 weeks after completion of neoadjuvant chemotherapy, patients receive paclitaxel IV over 1 hour twice weekly and undergo radiotherapy once daily, 5 days a week, for 6½ weeks.
• Surgery: At 6-8 weeks after completion of chemoradiotherapy, patients undergo surgical resection (e.g., modified radical mastectomy or lumpectomy and axillary node dissection).
• Adjuvant chemotherapy: Beginning 4-6 weeks after surgery, patients receive doxorubicin hydrochloride IV over 20 minutes and cyclophosphamide IV over 1 hour on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
• Hormonal therapy: After completion of adjuvant chemotherapy, patients with estrogen receptor- and/or progesterone receptor-positive tumor receive hormonal therapy at the discretion of the treating physician.

Patients undergo blood and tissue sample collection periodically to analyze changes in cell cycle by flow cytometry; antibody assays; kinase assays for cyclin B1/CDC2; genetic assays for p53, p21, and other molecular markers; and protein expression assays by mass spectrometry.

After completion of study therapy, patients are followed periodically.

DISEASE CHARACTERISTICS:

• Histologically or cytologically documented invasive carcinoma of the breast*

• Tumor ≥ 2 cm in greatest dimension (e.g., T2-4) and any nodal status (e.g., N0-3), including locally advanced disease, as defined by the following criteria:

• Primary tumor ≥ 5 cm
• Tumor of any size with direct extension to the chest wall or skin
• Inflammatory breast cancer (T4d)
• Metastasis to ipsilateral internal mammary node
• Ipsilateral lymph nodes that are clinically fixed to each other or to other structures (N2) NOTE: *Diagnosis may be made by core or tru-cut biopsies
• Measurable or evaluable tumor

• Measurable disease is defined as any mass that can be reproducibly measured in two perpendicular dimensions
• Evaluable disease is defined as any lesion visible by mammogram or palpable by physical exam that does not fit the above criteria of measurability
• Planning to undergo breast conservation surgery
• Willing to undergo AND is a candidate for radiotherapy, in the judgement of the treating radiation oncologist
• No evidence of distant metastatic disease (e.g., lung, liver, bone, brain)
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Menopausal status not specified
• ECOG performance status 0-1
• WBC ≥ 3,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• Left ventricular ejection fraction ≥ 45%
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancies within the past 5 years, except curatively treated nonmelanomatous skin cancer or carcinoma in situ of the cervix
• No history of hypersensitivity reaction to products containing polysorbate 80 (Tween 80)
• No serious medical illness that, in the judgment of the treating physician, places the patient at risk
• No peripheral neuropathy ≥ grade 2

PRIOR CONCURRENT THERAPY:

• Prior tamoxifen as chemoprevention allowed
• No prior radiotherapy to the ipsilateral breast

• Prior radiotherapy to the contralateral breast is allowed
• No prior chemotherapy