2026 Proffered Presentations
S147: MENINGIOMAS AND BREAST CANCER: RNA-GUIDED EXPLORATION
Harsh P Shah, MD, MPI1; Yogesh Rakholia2; Hayden M Dux2; Selvaraj Muthusamy, MBBS, PhD2; Hope Richard, MD, PhD2; William C Broaddus, MD, PhD2; 1Washington University in St. Louis, Virginia Commonwealth University; 2Virginia Commonwealth University
Objective: To determine whether meningiomas arising in patients with a history of breast cancer harbor distinct transcriptomic features compared with meningiomas from patients without breast cancer, and to identify candidate pathways that might explain the observed clinical association.
Background: Meningiomas are the most common primary central nervous system tumors in adults, comprising 36% of new diagnoses. Breast cancer is the most common cancer diagnosis in the United States, affecting 13% of American women. Epidemiologic studies have long suggested a clinical association between meningioma and breast cancer, but causality and underlying biology remain uncertain.
Methods: Patients who underwent surgical resection for histopathologically-confirmed meningioma with a history of breast cancer from 2001 to 2020 at a single academic center were identified via a retrospective query of an internal cancer registry. Endogenous mRNA sequencing using NanoString (Seattle, WA) targeted gene-expression panel was performed on surgical pathology speciemns obtained from meningioma resections. Copy number variant (CNV) analysis was performed using nSolver 4.0.70. Gene enrichment was analyzed using the Database for Annotation Visualization and Integrated Discovery (DAVID). Retrospective chart review was performed on all included patients to obtain demographic and clinical data. Benjamini-Yekutieli correction was applied for multiple comparisons.
Results: Total of twenty-nine meningioma samples were included in the final analysis, sixteen from patients with meningioma and breast cancer and thirteen from patients with meningioma. Demographic data and clinical outcomes are included in Table 1. No significant differences were noted in the meningioma grades. Differentially expressed genes between the two cohorts of meningiomas with corrected p-value < 0.05 are included in Figure 1 and Table 2. Expression of BCL2-associated agonist of cell death (BAD), eukaryotic translation initiation factor 4 gamma 1 (EIF4G1), 3-phosphoinositide dependent protein kinase 1 (PDPK1), ras homolog, mTORC1 binding (RHEB), ribosomal protein S6 kinase A1 (RPS6KA1), and APC regulator of WNT signaling pathway (APC) was increased in meningiomas from patients who also had breast cancer while Integrin subunit beta 1 (ITGB1) expression was increased in patients with meningioma alone. Log2 Fold Change values were highest for RHEB (0.937), BAD (0.845), and RPS6KA1 (0.789). Gene ontology pathway analysis implicates protein kinase binding, PI3K-Akt signaling, and hormonal signaling pathways.
Conclusions: Meningiomas from patients with breast cancer demonstrate transcriptomic differences suggestive of altered hormonal and protein-kinase triggered cellular signaling. These findings may provide a biological framework for the longstanding epidemiologic link between meningioma and breast cancer. Expanded analytic cohorts, analysis of breast cancer samples, and prospectively captured data will serve as key next steps to further validate these findings. Therapeutic strategies to target implicated gene pathways may provide novel avenues for treating skull base and non-skull base meningiomas, along with informing individualized counseling and surveillance for patients.
Table 1
Figure 1
Table 2
