[287] Folate Receptor alpha Is Frequently Expressed in ER/PR Negative and Triple Negative Breast Cancers

David Tacha, Ryan Bremer. Biocare Medical, LLC, Concord, CA

Background: Folate receptor alpha (FRA) is a membrane-attached protein that facilitates transport of folate, and has been found to be overexpressed in several cancers, including lung, ovarian and breast cancers. In a previous immunohistochemical study, overexpression of FRA in breast cancer strongly correlated with early recurrence and decreased median survival. As a result, FRA has emerged as a potential therapeutic target. A humanized monoclonal antibody to FRA (Farletuzumab) in currently in development and may be an attractive treatment strategy either alone or combined with chemotherapy.
Design: A new, highly specific clone of an anti-FRA antibody, [26B3.F2], suitable for immunohistochemistry, has recently been developed and characterized on formalin-fixed paraffin-embedded tissue. 26B3 was optimally tittered and applied to 67 cases of breast cancer, with previously determined ER, PR and Her2 status. Only membrane staining of FRA was considered positive, with a cut-off point of 10% of tumor cells staining.
Results: Of the 67 cases of invasive ductal carcinoma stained with 26B3, 20 were positive for FRA expression. Significantly, a higher incidence of expression of FRA was observed in hormone receptor negative patients (ER-/PR-), independent of Her2 status (Table 1, p=0.03). Only 4/27 (14.8%) specimens positive for ER and PR were also positive for FRA; whereas 16/40 (40.0%) specimens negative for ER and PR expressed FRA.

Table 1: FRA Expression and ER/PR/Her2 Status
 ER+/PR+, Her2+/-ER-/PR-, Her2+/-
FRA +416
FRA -2324
% FRA +14.8%40.0%

Importantly, half of all triple negative specimens (9/18, 50.0%) were positive for FRA, a significant increase over FRA expression in specimens that were ER/PR and/or Her2 positive (11/49, 22.4%) (Table 2, p=0.04).

Table 2: FRA Expression in Triple Negative Breast Cancers
 ER+/PR+ or Her2+ER-/PR- Her2- (Triple Negative)
FRA +119
FRA -389
% FRA +22.4%50.0%

Conclusions: FRA expression has been identified in 30% (20/67) of breast cancers, with an increased incidence in ER/PR negative cases. Significantly, 50% (9/18) of triple negative breast cancers were positive for FRA expression. Determining positive FRA expression in breast cancers may identify patients that would benefit from an anti-folate targeted therapy, including hormone receptor or Her2 positive patients that have failed to respond to prior treatment, or triple negative patients, for whom limited treatment options are available.
Category: Breast

Tuesday, March 5, 2013 9:30 AM

Poster Session III # 21, Tuesday Morning


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