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

Nadine Norton, Bahaaeldin Youssef, David W. Hillman, Aziza Nassar, Xochiquetzal J Geiger, Brian M. Necela, Heshan Liu, Kathryn J. Ruddy, Mei Yin C. Polley, James N. Ingle, Fergus J. Couch, Edith A. Perez, Minetta C. Liu, Jodi M. Carter, Roberto A. Leon-Ferre, Judy C. Boughey, Elizabeth B. Somers, Krishna R. Kalari, Daniel W. Visscher, Matthew P. GoetzKeith L. Knutson

Research output: Contribution to journalArticle

1 Scopus citations


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 (FRα) is significantly increased in patients with TNBC and is therefore a potential biomarker and therapeutic target. We optimized and validated a FRα immunohistochemistry method, specific to TNBC, to measure FRα 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 FRα IHC demonstrated exceptional performance characteristics with low intra- and interassay variability as well as minimal lot-to-lot variation. FRα 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, FRα expression was associated with improved IDFS (HR = 0.63, p = 0.01) but not with OS. The results demonstrate the potential of targeting the FRα in the majority of TNBC patients and suggest that variable expression may point to a need to stratify on FRα expression in clinical studies.

Original languageEnglish (US)
Article number4
Journalnpj Breast Cancer
Issue number1
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology (medical)

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