Brain metastases in breast cancer and Ki67 expression.

Abstract

e21018 Background: Ten to 15% of patients (pts) with breast cancer (BC) will be diagnosed with central nervous system (CNS) metastases, and autopsy series suggest that up to 30% of pts have evidence of CNS disease at the time of death. The identification of factors influencing prognosis may help lead to possibly improve the disease management. Methods: BC pts with CNS metastases were identified within a database of 1,609 BC diagnoses from 1995 to 2010 at the Department of Oncology, Azienda ULSS 13 VE. Pathologic features of tumor samples were examined using standard immune-histochemical assays. Results: Seventy-two pts with CNS metastases were identified. Median age at primary BC diagnosis was 49 years (range, 28-81); median time to CNS metastases was 44 months (range, 0-244). HER2 overexpression was found in tumors from 34 pts (47.2%); 27 pts (37.5%) had tumors lacking overexpression of HER2, estrogen receptors (ER), and progesterone receptors (PgR) (TNBC). Overexpression of p53 (at least 20% tumor cells positive), Ki67 (at least 20%), and BCL2 (at least 30%) were detected in tumors from 22 pts (30.6%), 41 pts (56.9%), and 22 pts (30.6%), respectively. Median survival from CNS involvement was 3.8 months (95% CI 2.72-4.88), with 21.6% and 12.0% of patients estimated to be alive at 12 and 24 months, respectively (Kaplan-Meier product limit method). At univariate log-rank analysis TNBC had a significant poorer survival than HER2 positive patients (3.8 vs 16.6 months) only in the Ki67-negative cohort. The Cox proportional hazards analysis found that Ki67 overexpression and age at diagnosis >50 years were the only factors independently associated with a increased risk of death (2.5-fold and 2.2-fold increase, respectively [Table]). Conclusions: In our series of BC pts with CNS metastases, 85% of patients had either HER2 overexpression or TNB, Ki67 being the prognostic discriminant for survival, mainly in the HER2-positive cohort. Beta SE(beta) Exp(beta) 95%CL (exp)beta)) P TNBC .510 .462 1.665 .674 to 4.113 .270 HER2 positive -.646 .447 .524 .218 to 1.258 .148 P53 positive -1.999 .304 .512 .452 to 1.486 .819 Ki67 positive .911 .312 2.488 1.349 to 4.588 .004 BCL2 positive -.308 .331 .735 .384 to 1.407 .352 Age >50 .800 .313 2.225 1.204 to 4.112 .011