Clinical, pathological and immunistochemistry characterization of primary breast cancer metastasizing to the central nervous system (CNS): Analysis of time to development of CNS metastasis

Abstract

2051 Background: The characterization of breast cancer patients (BCP) with high risk of developing CNS metastases still remains a challenge. The identification of these patients could enable new strategies of prevention, early detection and innovative treatments. Methods: We analyzed the records of 950 BCP treated at our institutions during 1997 to 2003 and found that 38 (4%) of these patients developed CNS metastases. In these 38 patients, we reviewed the clinical course, initial pathology and the primary tumor immunohistochemistry profile of hormone receptors, HER-2, p53, as well as microvessel density by the Chalkey count technique by the anti-CD105 antibody E-9. Results: Median age was 54 years (30–75), 11% < 40 years, median tumor size was 3.5 cm (1.2–17). Median number of positive axillary nodes was 6 (0–27) and axillary lymph nodes were negative in 10 patients (29%). Only two patients (5%) had grade 1 tumors. The median survival after the development of CNS metastases was of 4.5 months (0.5 - 27 months), with 8% of patients living longer than one year. Treatment consisted of whole brain radiotherapy in 79% of the patients. Hormone negative receptor status was found in 24 patients (63%), HER-2 was overexpressed in 26 patients (68%) and p53 was positive in 16 patients (46%). Mean Microvessel density was > 7 in 23 patients (59%). For the whole group of patients, the median time to the development of CNS metastases was 22 months (5–96). Patients with p53 positive tumors had a lower time to development of CNS metastasis (19.3 versus 34.6 months, p = 0.005), as compared to p53 negative tumors. No differences were found between subgroups of patients, as defined by tumor grade, microvessel density, hormone receptors and HER-2 status, or positivity of axyllary lymph nodes. Conclusions: The primary tumors of BCP who developed CNS metastases showed a high percentage of hormonoreceptor negativity (63%), overexpression of HER-2 (68%), and high counts of microvessel density . While the role of CD 105 expression and the development of CNS metastases in BC patients deserve further research, p53 positivity may be a marker of risk of early development of CNS metastases in BCP. No significant financial relationships to disclose.