Radiation Therapy to the Head in Preventing Brain Metastases in Women Receiving Trastuzumab and Chemotherapy for Metastatic or Locally Advanced Breast Cancer

OBJECTIVES:

• To test if prophylactic cranial radiotherapy delivering 30 Gy in 10 fractions will significantly reduce (from 35% to 21% at 2 years) the incidence of symptomatic brain metastases in patients treated with trastuzumab (Herceptin®) for metastatic breast cancer.

OUTLINE: This is a multicenter study. Patients are stratified by center, type of systemic therapy (trastuzumab [Herceptin®] monotherapy vs combination with chemotherapy), hormone receptor status, and presence of lung metastases (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive taxane/trastuzumab therapy for 6 weeks. While continuing taxane/trastuzumab therapy, patients then undergo 10 fractions of concurrent prophylactic cranial radiotherapy in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive taxane/trastuzumab therapy without concurrent prophylactic cranial radiotherapy.

All patients undergo quality of life assessments every 8 weeks for 9 months.

After completion of study treatment, patients are followed periodically for at least 1 year.

DISEASE CHARACTERISTICS:

• Histologically proven breast carcinoma

• Metastatic or locally advanced disease
• Must demonstrate HER2 3+ positivity on IHC or 2+ over-expression and FISH test demonstrating C-erB2 gene amplification
• No known or suspected brain metastases or CNS disease, as defined by the presence of any of the following key symptoms:

• Headache
• Nausea and/or vomiting
• Clinical signs of raised intracranial pressure
• Seizures
• Focal symptoms
• Cognitive dysfunction
• Affective disorder
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Female
• Postmenopausal status not specified
• ECOG performance status 0 or 1
• Patients must a-priori be suitable for trastuzumab (Herceptin®) +/- chemotherapy in terms of bone marrow, hepatic, and renal function
• No prior history of cerebrovascular disease or neurological disorder including seizures

PRIOR CONCURRENT THERAPY:

• No prior cranial radiotherapy
• No prior neurosurgery