Folate receptor alpha expression associates with improved disease-free survival in triple negative breast cancer patients

Triple negative breast cancer (TNBC) comprises 15-20% of all invasive breast cancer and is associated with a poor prognosis. As therapy options are limited for this subtype, there is a significant need to identify new targeted approaches for TNBC patient management. The expression of the folate receptor alpha (FR alpha) is significantly increased in patients with TNBC and is therefore a potential biomarker and therapeutic target. We optimized and validated a FR alpha immunohistochemistry method, specific to TNBC, to measure FR alpha expression in a centrally confirmed cohort of 384 patients with TNBC in order to determine if expression of the protein is associated with invasive disease-free survival (IDFS) and overall survival (OS). The FR alpha IHC demonstrated exceptional performance characteristics with low intra- and interassay variability as well as minimal lot-to-lot variation. FR alpha expression, which varied widely from sample to sample, was detected in 274 (71%) of the TNBC lesions. In a multivariable model adjusted for baseline characteristics, FR alpha expression was associated with improved IDFS (HR = 0.63, p = 0.01) but not with OS. The results demonstrate the potential of targeting the FR alpha in the majority of TNBC patients and suggest that variable expression may point to a need to stratify on FR alpha expression in clinical studies.