Trastuzumab for 6 Months or 1 Year in Treating Women With Nonmetastatic Breast Cancer That Can Be Removed By Surgery

OBJECTIVES:

Primary

• Compare the disease-free survival of women with nonmetastatic, resectable breast cancer treated with adjuvant trastuzumab (Herceptin®) for 6 months vs 12 months.

Secondary

• Compare cardiotoxicity in patients receiving these regimens.
• Compare the cardiotoxicity and disease-free survival of patients receiving concurrent trastuzumab and chemotherapy vs sequential administration.
• Correlate HER-2 polymorphism with disease-free survival/cardiotoxicity in these patients.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to participating center, modality of adjuvant chemotherapy (concurrent vs sequential), and adjuvant hormonal therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I (control arm, 12-month therapy): Patients continue to receive trastuzumab (Herceptin®) IV until a total of 12 months of therapy is completed in the absence of disease progression or unacceptable toxicity.
• Arm II (experimental arm, 6-month therapy): Patients continue to receive trastuzumab* IV until a total of 6 months of therapy is completed in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients who have already finished 6 months of trastuzumab at randomization do not receive further trastuzumab.

Some patients undergo blood collection for HER-2 polymorphism analysis.

After completion of study therapy, patients are followed periodically for approximately 5 years.

PROJECTED ACCRUAL: A total of 7,000 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the breast
• Nonmetastatic disease

• Positive or negative axillary nodes
• Tumor size ≥ 10 mm
• Resectable disease
• Must have received ≥ 4 courses of chemotherapy for this disease
• A 12-month adjuvant treatment with trastuzumab (Herceptin®) has been initiated

• Informed consent form must be signed between the third and sixth months of trastuzumab therapy
• Overexpression of HER-2 in the invasive component of the primary tumor as indicated by 1 of the following:

• 3+ by immunohistochemistry (IHC)
• 2+ by IHC and confirmation by fluorescent in situ hybridization (FISH) or chromogenic in situ hybridization (CISH)
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Female
• Menopausal status not specified
• LVEF considered favorable for continuing trastuzumab treatment as measured by echocardiography or MUGA at 2-4 months after beginning adjuvant trastuzumab
• No serious cardiac illness or medical condition precluding trastuzumab treatment, including any of the following:

• History of documented congestive heart failure
• High-risk uncontrolled arrhythmias
• Angina pectoris requiring antianginal medication
• Severe dyspnea at rest or oxygen-dependent
• No known hypersensitivity to trastuzumab, murine proteins, or any of the excipients
• Not pregnant or nursing
• No social, geographical, or psychological condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Other prior anti-HER-2 therapy allowed
• No prior trastuzumab other than initiation of trastuzumab adjuvant therapy