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 journalArticlepeer-review

9 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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