[4003] Clinical and pathologic characteristics of brain metastases of breast carcinoma: a study of 74 patients.

Brogi E, Murray MP, Nehhozina T, Akram M, Cranor M, Seidman A.. Memorial Sloan-Kettering Cancer Center, New York, NY

Background: Brain metastases (BM) of breast carcinoma (BC) are notable for symptom severity, limited treatment options and generally poor prognosis. Study of the clinical and pathological features of BM of BC could identify parameters useful for disease prognostication and treatment.
Material and Methods: Search of our pathology files identified 74 patients with biopsy-proven BM of BC treated at our institution from 1992 to 2006. Clinical and pathologic data were retrieved from the medical records. A BM tissue microarray (TMA) was constructed and used for detection of ER, PR, Her-2. We also evaluated immunoreactivity for EGFR, c-kit, CK5/6, 4A4 and calponin, a panel of antigens that has been correlated with basal-like gene profile of BC.
Results: All 74 patients were women. The median age at diagnosis (DX) of BC was 45 y (range 31-76), with 18 patients <40 y at presentation. Per report, invasive BC was ductal in 61 cases, lobular in 3, had mixed ductal and lobular features in one case and high grade neuroendocrine morphology in another; no histology information was available in 8 cases. Patient median age at DX of BM was 51 y (range 32-83) and the median interval since BC DX was 41 m (range 2 m -23 y). BM were supratentorial in 49 patients and infratentorial in 24; one patient had both supra- and infratentorial tumors. Forty-one patients had developed skeletal metastases, 37 pulmonary and 37 hepatic; 17 patients had metastases to all of the above sites. Fifty-four patients died of disease after a median interval of 10 m since DX of BM (range 1-66); 14 are alive with disease and 6 are lost to follow-up. Immunostains on the BM TMA showed that 41% of cases were ER, PR and Her-2(-) (triple negative); 37% Her-2(+); 26% ER(+) and 8% PR(+). Weak to moderate reactivity for EGFR was noted in 32% of cases; focal positivity for CK5/6 in 29%; nuclear reactivity for 4A4 in 3%; no case was positive for calponin and c-kit. Only 5 cases were triple negative and immunoreactive for EGFR and cytokeratin 5/6, an immunoprofile that has been correlated with basal-like BC. We also noted that 91% of infratentorial metastases were ER(-), in contrast to 65% of supratentorial tumors; one patient with supra- and infratentorial lesions had an ER(-) carcinoma. Median survival since DX of BM was 15 months (range 1-41) for patients with infratentorial lesions versus 10.5 months (range 1-77) for patients with supratentorial BM. Discussion: We found that most BM of BC are either Her-2(+) or triple negative. In the latter group, only few tumors showed an immunoprofile consistent with basal-like carcinoma. In addition, most of the infratentorial BM of BC in our study were ER(-). Evaluation of additional BM and matched primary BC is in progress. The results of our study will contribute to better understanding the biology of BM of BC and may help to identify targets relevant for treatment. Support: Department of Defense COE Grant #BC050006.

Saturday, December 16, 2006 7:00 AM

Poster Session IV: Detection and Diagnosis: Diagnostic Pathology (7:00 AM-9:00 AM)