Molecular Profile of Breast Cancer Metastases to the Central Nervous System
N Alberti, D Val, J Vicens, MF Garijo, JF Val-Bernal, P de Agustin, MJ Merino. National Cancer Institute, Bethesda, MD; Marques de Valdecilla University Hospital, Santander, Spain; 12 de Octubre University Hospital, Madrid, Spain
Background: Breast cancer (BC) is the second most common cause of central nervous system (CNS) metastases, developing in 10-20% of patients with BC. Previous studies have suggested that patients with positive HER2 status BC developed CNS metastases within 16 months, thus, development of new molecular therapies that interfere with HER2 pathways are needed. We studied primary tumors and corresponding CNS metastasis of patients with BC to compare the expression of molecular markers (ER/PR, HER2, EGFR) in both locations and to identify molecular profile of primary BC which could indicate an increased risk for spread to the CNS.
Design: Twenty patients with primary BC and their corresponding CNS metastases were studied. Clinical data and pathologic features were reviewed. Treatment of primary BC included surgery, chemotherapy and radiation. All cases were evaluated for estrogens-(ER)/progesterone-(PR) receptors, HER2 and EGFR expression by immunohistochemistry (IHC). HER2 status was also evaluated by chromogenic in situ hybridization (CISH).
Results: Patients had an average age of 47 years (range 27-70years). All primary tumors were invasive ductal carcinomas, of moderate (35%) and high histologic grade (65%). Primary BC show negative ER/PR, positive EGFR and positive HER2 status in 56%, 31%, and 30% of cases respectively. A 56 % of tumors expressed positive EGFR and/or HER2 status with negative ER/PR. CNS metastases had the same ER/PR, EGFR and HER2 status as the primary tumors in 95%, 80% and 95% of cases respectively. In both primary and metastatic lesions, we found high concordance between IHC and CISH in HER2 status testing. All IHC negative (0/1+) and positive (3+) cases were unamplified and amplified by CISH respectively. IHC-equivocal (2+) results were found in 7/40 (17%) samples, corresponding to 5 primary and 2 metastatic tumors. In these cases, CISH confirmed gene amplification in 2 primary lesions and nonamplification in the remaining five tumors.
Conclusions: Our study suggests that patients affected by primary BC with negative ER/PR and positive HER2 or EGFR status are more susceptible to develop metastases to the CNS. Molecular profile of the primary tumor has been maintained in the CNS metastasis.
Monday, March 9, 2009 1:00 PM
Poster Session II # 50, Monday Afternoon