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SDPS-46 CENTRAL NERVOUS SYSTEM (CNS)-RELATED MORTALITY IN PATIENTS WITH HER2-POSITIVE METASTATIC BREAST CANCER

BACKGROUND: Approximately one third of patients with HER2-positive (+) metastatic breast cancer (MBC) develop brain metastases (BrM). In light of discordant control of extracranial metastases (ECM) versus BrM for standard-of-care antibody-based therapies for these patients, and the frequent use of r...

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Autores principales: Ferraro, Emanuela, Nassif, Rabih Bou, Reiner, Anne, Tosi, Umberto, Panageas, Katherine, Dang, Chau T, Seidman, Andrew D, Moss, Nelson
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10402311/
http://dx.doi.org/10.1093/noajnl/vdad070.100
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author Ferraro, Emanuela
Nassif, Rabih Bou
Reiner, Anne
Tosi, Umberto
Panageas, Katherine
Dang, Chau T
Seidman, Andrew D
Moss, Nelson
author_facet Ferraro, Emanuela
Nassif, Rabih Bou
Reiner, Anne
Tosi, Umberto
Panageas, Katherine
Dang, Chau T
Seidman, Andrew D
Moss, Nelson
author_sort Ferraro, Emanuela
collection PubMed
description BACKGROUND: Approximately one third of patients with HER2-positive (+) metastatic breast cancer (MBC) develop brain metastases (BrM). In light of discordant control of extracranial metastases (ECM) versus BrM for standard-of-care antibody-based therapies for these patients, and the frequent use of radiation and surgical therapies particularly for patients with CNS-centric disease, we sought to determine the proportion of HER2+ MBC patients with BrM who suffered neurologic death in the CNS-only and intracranial-plus-extracranial metastasis settings, and the clinical risk factors of such. METHODS: Clinicopathologic data for HER2+ MBC patients with BrM treated at an NCI-designated Comprehensive Cancer Center between August 2010 and April 2022 were collected, including disease burden at cancer presentation, the timing and pattern of BrM and ECM, and neurologic complications. CNS-related death was defined as any mortality caused by BrM, leptomeningeal progression, or BrM-associated complication. RESULTS: 275 patients were included. 58/275 (21%) presented with CNS as only and first site of metastasis; the remaining (217/275, 79%) developed BrM synchronously with or subsequent to ECM. 125/275 (45%) had de novo MBC, and nearly all patients were treated with CNS therapies (254/275 [92%] received at least one radiation treatment and 88/275 [32%] underwent BrM resection). After a median follow-up of 2.5 years, 193/275 (70%) patients died, of whom 105 (54%) of CNS-related cause. The median OS was 3 years (95% CI=1.47-5.14) and 2 years (95% CI=1.74-2.34) for patients with CNS-only versus BrM concurrently/subsequent to ECM, respectively (p=0.059). The cumulative incidence of CNS-related death at 5 years was 40% (95%CI=33-46%). CONCLUSIONS: Almost half of patients with HER2+ BrM suffered neurologic death. Patients with CNS-only disease had better OS than patients with synchronous/preceding ECM, suggesting that overall burden of disease affects mortality. With high rates of durable extracranial control with HER2-directed therapies, new strategies to prevent and eradicate CNS disease are urgent.
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spelling pubmed-104023112023-08-05 SDPS-46 CENTRAL NERVOUS SYSTEM (CNS)-RELATED MORTALITY IN PATIENTS WITH HER2-POSITIVE METASTATIC BREAST CANCER Ferraro, Emanuela Nassif, Rabih Bou Reiner, Anne Tosi, Umberto Panageas, Katherine Dang, Chau T Seidman, Andrew D Moss, Nelson Neurooncol Adv Final Category: Screening/Diagnostics/Prognostics BACKGROUND: Approximately one third of patients with HER2-positive (+) metastatic breast cancer (MBC) develop brain metastases (BrM). In light of discordant control of extracranial metastases (ECM) versus BrM for standard-of-care antibody-based therapies for these patients, and the frequent use of radiation and surgical therapies particularly for patients with CNS-centric disease, we sought to determine the proportion of HER2+ MBC patients with BrM who suffered neurologic death in the CNS-only and intracranial-plus-extracranial metastasis settings, and the clinical risk factors of such. METHODS: Clinicopathologic data for HER2+ MBC patients with BrM treated at an NCI-designated Comprehensive Cancer Center between August 2010 and April 2022 were collected, including disease burden at cancer presentation, the timing and pattern of BrM and ECM, and neurologic complications. CNS-related death was defined as any mortality caused by BrM, leptomeningeal progression, or BrM-associated complication. RESULTS: 275 patients were included. 58/275 (21%) presented with CNS as only and first site of metastasis; the remaining (217/275, 79%) developed BrM synchronously with or subsequent to ECM. 125/275 (45%) had de novo MBC, and nearly all patients were treated with CNS therapies (254/275 [92%] received at least one radiation treatment and 88/275 [32%] underwent BrM resection). After a median follow-up of 2.5 years, 193/275 (70%) patients died, of whom 105 (54%) of CNS-related cause. The median OS was 3 years (95% CI=1.47-5.14) and 2 years (95% CI=1.74-2.34) for patients with CNS-only versus BrM concurrently/subsequent to ECM, respectively (p=0.059). The cumulative incidence of CNS-related death at 5 years was 40% (95%CI=33-46%). CONCLUSIONS: Almost half of patients with HER2+ BrM suffered neurologic death. Patients with CNS-only disease had better OS than patients with synchronous/preceding ECM, suggesting that overall burden of disease affects mortality. With high rates of durable extracranial control with HER2-directed therapies, new strategies to prevent and eradicate CNS disease are urgent. Oxford University Press 2023-08-04 /pmc/articles/PMC10402311/ http://dx.doi.org/10.1093/noajnl/vdad070.100 Text en © The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Final Category: Screening/Diagnostics/Prognostics
Ferraro, Emanuela
Nassif, Rabih Bou
Reiner, Anne
Tosi, Umberto
Panageas, Katherine
Dang, Chau T
Seidman, Andrew D
Moss, Nelson
SDPS-46 CENTRAL NERVOUS SYSTEM (CNS)-RELATED MORTALITY IN PATIENTS WITH HER2-POSITIVE METASTATIC BREAST CANCER
title SDPS-46 CENTRAL NERVOUS SYSTEM (CNS)-RELATED MORTALITY IN PATIENTS WITH HER2-POSITIVE METASTATIC BREAST CANCER
title_full SDPS-46 CENTRAL NERVOUS SYSTEM (CNS)-RELATED MORTALITY IN PATIENTS WITH HER2-POSITIVE METASTATIC BREAST CANCER
title_fullStr SDPS-46 CENTRAL NERVOUS SYSTEM (CNS)-RELATED MORTALITY IN PATIENTS WITH HER2-POSITIVE METASTATIC BREAST CANCER
title_full_unstemmed SDPS-46 CENTRAL NERVOUS SYSTEM (CNS)-RELATED MORTALITY IN PATIENTS WITH HER2-POSITIVE METASTATIC BREAST CANCER
title_short SDPS-46 CENTRAL NERVOUS SYSTEM (CNS)-RELATED MORTALITY IN PATIENTS WITH HER2-POSITIVE METASTATIC BREAST CANCER
title_sort sdps-46 central nervous system (cns)-related mortality in patients with her2-positive metastatic breast cancer
topic Final Category: Screening/Diagnostics/Prognostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10402311/
http://dx.doi.org/10.1093/noajnl/vdad070.100
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