Abstract P6-01-15: Expression of high affinity folate receptor in breast cancer brain metastasis

Abstract

Abstract Background: Folic acid is required by proliferating cells for the synthesis of nucleotide bases among other tasks. The high affinity folate receptor (HFR) is a membrane protein that is upregulated in several cancers of epithelial origin and rarely present in most normal cells. High expression of HFR has been documented in ovarian, breast, kidney, uterine and lung cancers. In breast cancer patients, HFR is overexpressed in 33% of primary tumors (PT) and this is associated with poor prognosis. The HFR expression in breast cancer brain metastases (BCBM) is unknown. The aim of this study was to analyze the incidence of HFR expression in BCBM and its role in the prognosis of this high-risk patient subgroup. Methods: We analyzed a database of 42 patients who underwent craniotomy with resection of breast cancer brain metastasis (BCBM). Of those, we collected 19 brain metastasis (BM) and 13 PT. HFR status was assessed by immunohistochemistry. Log-Rank test analyzed differences in overall survival (OS) between groups. Results: Median age was 51 years (range 24-74). Median follow-up was 4.2 years (range 0.6-18.5). HFR was positive in 4/19 BM (21.1%) and in 1/13 PT (7.7%). Positive samples had low H-scores (range 1-50). Staining with H&E revealed that 11/19 BM (57.9%) and 7/13 PT (53.8%) had apocrine differentiation. Analysis of OS showed no difference between patients with positive HFR (median OS 48 months) and negative HFR (median OS 69 months) (P=0.25). Similarly, there was no difference in OS between patients with apocrine differentiation (median OS 63 months) and those without apocrine differentiation (median OS 69 months) (P=0.49). Conclusions: To the best of our knowledge, this is the first analysis of HFR expression in BCBM. While previous studies associated the presence of HFR with worse prognosis; in this cohort of high-risk patients, HFR was positive in only 21.1% of BM with low levels of positivity. Around half of our patients had apocrine differentiation. Neither the status of HFR nor the presence of apocrine features had impact in OS in our cohort. Citation Format: Jose P Leone, Rohit Bhargava, Adrian Lee, Adam Brufsky. Expression of high affinity folate receptor in breast cancer brain metastasis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-01-15.