HER-2/neu Status in Breast Cancer Metastases to the Central Nervous System

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Abstract
Context.—Breast cancer is lethal when it metastasizes; one frequent site for spread is the central nervous system (CNS). Approximately 15% to 30% of breast cancers overexpress the protein HER-2/neu at the primary site, but there are few data on whether metastases from these tumors overexpress HER-2/neu and might be responsive to the potentially toxic anti–HER-2/neu immunotherapy (trastuzumab [Herceptin]) used in patients with disseminated disease. Objective.—To assess CNS breast cancer metastases for HER-2/neu protein overexpression by immunohistochemistry and gene amplification by fluorescence in situ hybridization (FISH) and to compare the status in primary and metastatic sites in the same patient, whenever possible. Design.—Central nervous system breast cancer metastases (n = 53) from 33 patients and corresponding primary breast cancer specimens in a subset of these patients (n = 12) were retrospectively identified in surgical pathology and autopsy databases. Fluorescence in situ hybridization analysis using PathVysion probes for HER-2/neu and chromosome enumeration probe 17 (CEP 17) and immunohistochemistry using the c-Erb-B2 antibody (Dako A0485) were compared. Immunohistochemical sections were evaluated by both visual and image analysis techniques. Results.—Of 31 cases assessable by FISH, 26% showed gene amplification. One hundred percent concordance for HER-2/neu status was detected between the primary and CNS metastatic lesions in 10 of 10 patients analyzed by FISH; lesser concordance was noted in 12 cases compared by immunohistochemistry. In 9 patients with multiple CNS metastases, FISH showed concordance among different lesions within the same patient. Conclusions.—When FISH is the detection method, CNS metastases accurately reflect the HER-2/neu status of the primary tumor. Central nervous system metastases from breast cancer received as surgical specimens can therefore be used to assess HER-2/neu status in patients in whom the primary tumor is unavailable for analysis.