Expression of high affinity folate receptor in breast cancer brain metastasis

Abstract

High affinity folate receptor (HFR) can be overexpressed in breast cancer and is associated with poor prognosis, however the expression in breast cancer brain metastases (BCBM) is unknown. The aim of this study was to analyze the rate of HFR expression in BCBM and its role in the prognosis of this high-risk cohort. We analyzed 19 brain metastasis (BM) and 13 primary tumors (PT) from a total of 25 patients. HFR status was assessed by immunohistochemistry. 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). 56% of patients had apocrine differentiation. OS was similar between patients with positive HFR (median OS 48 months) and negative HFR (median OS 69 months) (P = 0.25); and between patients with apocrine differentiation (median OS 63 months) and those without apocrine differentiation (median OS 69 months) (P = 0.49). 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 our cohort HFR was positive in only 21.1% of BM with low levels of positivity. Neither HFR nor apocrine features had impact in OS.

Breast cancer brain metastases: the last frontier

“…The high affinity folate receptor (HFR) is a novel target present in 33 % of breast cancers for which there are available drugs being evaluated. Despite of the initial excitement, a recent study showed very low levels of expression in brain metastases [ 96 ]. Another approach that is currently under study in patients with breast cancer brain metastases is targeting the phosphatidylinositol 3-kinase (PI3K)—mammalian target of rapamycin (mTOR) pathway.…”

Hypocrellin B‐loaded, folate‐conjugated polymeric micelle for intraperitoneal targeting of ovarian cancer in vitro and in vivo

“…Furthermore, we selected folic acid as an active targeting molecule to enhance the tumor‐targeting effect. Folic acid can conjugate with folate receptor (FR), which is overexpressed in many types of tumors including ovarian, endometrial, breast, renal cell carcinomas, and so forth. Targeting the folate receptor has shown considerable promise in mediating uptake of a variety of drugs, gene therapy products, and radiopharmaceuticals …”

Rational design of block copolymer self-assemblies in photodynamic therapy

“…Folate (FA) has been extensively studied as a targeting moiety [116] due to the overexpression of folate receptors in a number of tumor types including ovarian [117] or breast cancers [118]. One of the most recent examples of FA use in PDT applications is by Li et al, where the authors have designed a FA-PEO-PLA construct to deliver hypocrellin B, a sensitizer extracted from fungi, to intraperitoneal tumors [39].…”