Risk of seizures in a population of women with BRCA-positive metastatic breast cancer in the United States.

Abstract

e13056 Background: Real-world evidence on the risk of seizures in subgroups of women with advanced breast cancer (BC) across treatment-related or clinical subtypes is limited. A large electronic health record (EHR) dataset was used in this study to measure incidence and risk factors for seizures among women diagnosed with BRCA-associated metastatic BC (mBC). Methods: We used the Optum EHR database, which includes natural language processing (NLP) abstracted details from physicians’ notes, to identify a cohort of females with mBC (based on secondary malignancy ICD-9/-10 codes or NLP) diagnosed between 2008-2018 with 12 months of pre-index history, evidence of BRCA mutation positive (BRCA+) status, and no history of prior cancers. Analyses were stratified by the overall BRCA+ cohort and 4 molecular phenotypes: HER2+/HR-, HER2-/HR+, HER2+/HR+, and triple negative BC (TNBC). Incidence of seizures was measured using diagnosis codes and NLP, and incidence rates were calculated as the number of women with a seizure over the period from metastasis to first seizure or the end of follow up. Incidence rates were also measured across the following risk factors: PARP inhibitor use, diagnosed brain metastases, history of seizures, and anticonvulsant use before BC diagnosis, while controlling for age at metastasis, number of prior lines, and metastasis location. Results: Of the 7,941 BRCA+ patients identified, 27.8% had ≥1 seizure during mean follow-up of 2.35 years, with an incidence rate of 11.83 (95% CI: 11.35-12.33) per 100 person-years. The HER2-/HR+ and TNBC subgroups 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]). Kaplan-Meier analysis of time to seizure showed that HR- phenotype was associated with a longer time to first seizure. Patients with diagnosed brain metastases or a history of seizures had higher seizure incidence rates compared to patients without the respective risk factors (42.55 [95% CI: 28.59-63.30] vs 5.26 [4.20-6.59] and 34.76 [23.24-52.01] vs 6.35 [5.11-7.88]). Incidence trended higher with PARP inhibitor use, but patient numbers were low. Conclusions: Using both diagnosis codes and NLP, this study shows that seizures occur frequently in women with BRCA+ mBC, even those without diagnosed brain metastases. The seizure incidence rates by phenotype underscore their relevance when assessing seizure risk. These findings may have implications for clinical practice and for assessing benefit-risk ratios of novel agents.[Table: see text]