Characteristics of patients with brain metastases receiving trastuzumab for HER2 overexpressing metastatic breast cancer.

The intention of this retrospective analysis was to describe the characteristics of patients with brain metastasis (BM) receiving trastuzumab for HER2 overexpressing metastatic breast cancer (MBC). A specific focus was the relation of BM occurrence to remission status of visceral disease during trastuzumab treatment. Patients with MBC presenting between March 2000 and May 2004 were included in this retrospective analysis. HER2 overexpression was determined by immunohistochemistry (IHC; DAKO Hercep Test). Trastuzumab was applied at a loading dose of 4 mg/kg and a maintenance dose of 2 mg/kg. Among 136 HER2 overexpressing patients (DAKO score 3+), 42 patients with BM were identified during follow-up (30.9%). Negative hormone receptor expression (estrogen receptor (ER) and progesterone receptor (PgR)) correlated with incidence of BM (42.8% vs. 23.4%; P=0.01). There was no correlation of the development of BM with regard to tumor grading and patient age. In patients who developed BM, the median interval between visceral and brain metastasis was 14 months (range 0-69 months). At the time BM was diagnosed, 14 out of 42 patients responded to trastuzumab-based treatment schedules (OR: 33.3%, 95% CI 18.5-48.2%). Median survival from diagnosis of BM was 13 months (range 0-60 months). The median overall survival calculated from first diagnosis of metastasis was not significantly shorter in patients with BM than in patients without BM (37 vs. 47 months; P=0.07 log rank). Trastuzumab is highly effective for the treatment of liver and lung metastasis in HER2 overexpressing patients, while it is apparently ineffective for treating or preventing BM. Since one third of HER2 overexpressing patients with MBC developed BM despite effective trastuzumab treatment, new treatment strategies and closer surveillance may be warranted for these patients.