[2039] Cerebral metastasis in advanced breast cancer and the significance of HER2 status.

Kristiansen C, Enevoldsen K, Langkjer ST.. Vejle Hospital, Vejle, Denmark

Background: As many as one third of women with disseminated breast cancer develop cerebral metastasis. HER2 over-expression is found in 20-30% of breast cancer patients and several studies has reported a high incidence of cerebral metastasis among HER2 positive patients. Our aim was to evaluate the significance of HER2 over-expression among patients with advanced breast cancer and the incidence, pattern and timing of cerebral metastases when compared to similar patients without HER2 over-expression.
Material and Methods: Two patient cohorts were examined retrospectively. The first group consisted of 36 patients diagnosed with advanced breast cancer and over-expression of HER2 status who entered the phase 2 study with trastuzumab and paclitaxel either as first or second line chemotherapy. Patients were included between November 2001 and October 2005. The second group consisted of 42 patients with normal HER2 status and diagnosed with advanced breast cancer entering a study with same inclusion criteria as above except they had not HER2 over-expression. They were randomized between docetaxel or docetaxel and gemcitabin either as first or second line chemotherapy. Patients were included between January 2003 and September 2005.
Results: Eighteen of the 36 HER2 over-expression patients were diagnosed with cerebral metastases (0.50) during follow-up time of 1.4 years (range 0.4-3.2) compared to 6 patients (0.1) (p=0.0003) among the 42 patients with normal HER2 status with a median follow-up time of 1.3 years (range 0.5-3.0). The median age when included in protocol was 57.2 years (range 35.9-74.7) for the HER2 positive patients and 60.9 years (range 44.4-70.0) for patients without HER2 over-expression, not significant. Median time to cerebral metastases from inclusion was 0.8 years (range 0.5-2.7) for patients with HER2 over-expression and 1.0 years (range 0.1-2.5) for patients without, not significant. The median survival time from the diagnoses of cerebral metastases to end of follow-up were 0.3 years (range 0.1-1.0) for patients with HER2 over-expression and 0.3 (range 0.1-0.7) for patients without. Twenty-one of the patients had died during follow-up (0.6) among the HER2 positive patients and 15 (0.4) in the other group (p=0.05). In both groups all patients with cerebral metastases had multiple cerebral metastases and received radiotherapy.
Discussion: Our study shows that HER2 over-expression increases the risk of cerebral metastases significantly as compared to patients without HER2 over-expression. Brain metastases are seen earlier among patients with HER2 over-expression than among HER2 negative patients, though not significant. The median survival time for patients with cerebral metastases is poor. Since half of HER2 over-expressing patients developed brain-metastases close surveillance for brain metastases (clinical and/or imaging) is necessary even during effective systemic treatment. Future investigation into prophylactic cranial irradiation strategies in high-risk patients is warranted.

Friday, December 15, 2006 7:00 AM

Poster Session II: Prognosis and Response Prediction: Prognostic Factors I (7:00 AM-9:00 AM)