Central nervous system progression during systemic response to trastuzumab, humanized anti-HER-2/neu antibody, plus paclitaxel in a woman with refractory metastatic breast cancer

Treatment of selected patients with anti-HER-2/neu antibodies alone (1) or in combination with chemotherapy (2) may be of benefit to patients with refractory breast cancer. Approximately 30% of breast cancers overexpress HER-2/neu, a member of the epidermal growth factor receptor family. These patients may have a poorer overall prognosis (3) due to relative resistance to both hormonal therapy and chemotherapy (4-6). We recently observed a patient with refractory breast cancer who responded to rhuMAB HER-2 (trastuzumab) plus paclitaxel after progressing on paclitaxel alone. While on combination treatment she developed cerebellar metastases. Follow-up computed tomography (CT) scan revealed that her disease continued to respond in the liver, lungs, and bone. This case suggests that failure of trastuzumab to cross the blood-brain barrier may compromise its overall effectiveness and raises the possibility that the central nervous system (CNS), or other sanctuary sites, may become clinically more significant in patients with breast cancer in the era of antibody-based therapies.