Cross-sectional analysis reveals folate receptor alpha variation in ovarian cancer across age and race/ethnicity, suggesting broad clinical applicability.
Ovarian cancer (OC) is molecularly heterogeneous, requiring biomarkers to guide personalized therapy. Folate receptor alpha (FR⍺) is an actionable biomarker with therapeutic implications. We evaluated FR⍺ expression in OC by age, race/ethnicity, and histotype using real-world US clinicogenomic data. We conducted a cross-sectional analysis of patients diagnosed with ovarian, fallopian tube, or primary peritoneal cancer from 2019 to 2025 using the ConcertAI RWD360™ database linked to Caris Life Sciences genomic data. FR⍺ testing was done using the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay (Roche Diagnostics); FR⍺-high was defined as ≥75% of tumor cells with ≥2+ membrane staining. Stratified prevalence rates and multivariable prevalence rate ratios (RRs) with 95% CIs were estimated using modified Poisson regression. Sensitivity and exploratory analyses evaluated associations with FR⍺ expression in the full, unselected OC clinicogenomic database, applying a validated machine learning classifier trained on whole transcriptome RNAseq to predict FR⍺-high expression (N=3045). Among 1155 patients with OC who received FR⍺ testing, median age was 66 years (y) (IQR, 58-73); 71% were non-Hispanic White and 61% had high-grade serous histology. FR⍺-high expression was observed in 33%, with higher prevalence in high-grade serous (43%) compared to less common histotypes (low-grade serous, 24%; endometrioid, 6%; clear cell, 2%; carcinosarcoma, 9%) (P<0.001). There were no significant associations between FR⍺-high prevalence and age after adjusting for histotype (<50, Reference; 50-64, aRR 0.95, 95% CI 0.69-1.31; 65-74, aRR 1.15, 95% CI 0.84-1.57; ≥75 y, aRR 1.18, 95% CI 0.85-1.63). FR⍺-high prevalence did not differ by race/ethnicity (P=0.933) including after adjustment for age and histotype: non-Hispanic Black, 34% (aRR 1.03 [95% CI, 0.78-1.35]); non-Hispanic Asian, 29% (aRR 0.97, 95% CI 0.57-1.65); Hispanic, 30% (aRR 0.95, 95% CI 0.64-1.40); non-Hispanic White (32%, Reference). In sensitivity analyses restricted to high-grade serous histology, consistent associations with age and race/ethnicity were observed. In exploratory analyses, similar associations were observed in the broader database. FR⍺-high expression does not significantly differ by age or racial/ethnic group and is most prevalent in high-grade serous OC. These findings further support FR⍺ as an OC biomarker with broad clinical applicability across demographics and demonstrate the importance of accounting for potential confounding by histotype in studies of FR⍺-high prevalence. Further adoption of FR⍺ testing in the work-up for advanced OC provides important information to ensure patients have access to all eligible treatment options and biomarker-directed clinical trials, particularly for underrepresented groups and those facing disparities in access to healthcare. Citation Format: Rebecca C. Arend, Kent F. Hoskins, Jenny S. Guadamuz, Gregory S. Calip, Megan A. Clarke, Yookyung Christy Choi, Qu Zhang, Ricardo R. Lastra, Amanda L. Strickland, Sarah K. Lynam. Epidemiology of folate receptor alpha expression in ovarian cancer by age, race/ethnicity, and histotype in a real-world, US-based clinicogenomic database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5351.
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