Risk of seizures in a population of women with BRCA-positive metastatic breast cancer from an electronic health record database in the United States

BMC Cancer. 2023 Jan 24;23(1):78. doi: 10.1186/s12885-023-10554-6.


Background: Incidence and risk factors for seizures among women with advanced breast cancer (BC) and brain metastases are not well characterized across treatment-related or clinical subtypes. This study leveraged a large real-world dataset to describe incidence and risk factors for seizures in BRCA-associated metastatic breast cancer.

Methods: The Optum® de-identified electronic health records database was used. Females with a BC diagnoses between 2008 and 2018, with clinic visits 12 months before BC index date, evidence of BRCA mutation (BRCA+), evidence of metastasis, and no previous cancers were included. Analyses were stratified by the overall BRCA+ cohort and 4 molecular phenotypes: HER2+/HR- (human epidermal growth factor 2/hormone receptor), HER2-/HR+, HER2+/HR+, and triple negative BC (TNBC; HER2-/HR-). Seizures were identified using diagnosis codes and natural language processing. Incidence, occurrence rates, and cumulative incidence of seizures from the diagnosis of metastasis to the end of follow up were calculated. Comparisons were made between phenotypes and stratified on PARP inhibitor use, diagnosed brain metastases, history of seizures, and anticonvulsants use before BC. All comparisons included age at metastasis, number of prior lines of treatment, and metastasis location as covariates.

Results: 27.8% of 7941 BRCA+ patients had ≥1 seizure over a mean follow-up time of 2.35 years. Incidence and occurrence rates were 11.83 (95% CI: 11.35-12.33) and 201.3 (95% CI: 198.05-204.50), respectively, per 100 person-years. HER2-/HR+ and TNBC patients had the lowest and highest seizure incidence rates, respectively (10.94 [95% CI: 10.23-11.71] and 16.83 [95% CI: 15.34-18.46]). With HER2-/HR+ as the reference group in a competing risk analysis, TNBC (hazard ratio, HR = 1.35; 95%CI: 1.21, 1.52; p < 0.001) and HER2+/HR- (HR = 1.29; 95%CI: 1.07, 1.56; p < 0.01) patients had a greater risk of seizures. Patients with diagnosed brain metastases or a history of seizures had higher seizure rates. Incidence trended higher with PARP inhibitor use, but patient numbers were low.

Conclusions: This study provides novel real-world evidence on seizure incidence rates in BRCA+ BC patients, even those without diagnosed brain metastases, and underscores the need to understand patients' tumor phenotypes when assessing seizure risk. These findings may have implications for clinical practice and assessment of benefit-risk ratios of new therapeutic agents.

Keywords: BRCA-positive; Metastatic breast cancer; Predisposing factors; Seizures.

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Brain Neoplasms* / secondary
  • Breast Neoplasms* / pathology
  • Electronic Health Records
  • ErbB Receptors / therapeutic use
  • Female
  • Humans
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Receptor, ErbB-2 / therapeutic use
  • Retrospective Studies
  • Seizures / drug therapy
  • Triple Negative Breast Neoplasms* / drug therapy
  • United States


  • Poly(ADP-ribose) Polymerase Inhibitors
  • Antineoplastic Agents
  • ErbB Receptors
  • Receptor, ErbB-2

Supplementary concepts

  • Breast Cancer, Familial