Prevalence by therapy line and incidence of breast cancer brain metastases in 18,075 patients

Sarah L Sammons; Thibaut Sanglier; Jose Pablo Leone; Timothy K Erick; Peter Lambert; Filippo Montemurro; Raf Poppe; Eleonora Restuccia; Sara M Tolaney; Nancy U Lin

doi:10.1093/jnci/djaf048

Prevalence by therapy line and incidence of breast cancer brain metastases in 18,075 patients

J Natl Cancer Inst. 2025 Mar 31:djaf048. doi: 10.1093/jnci/djaf048. Online ahead of print.

Authors

Sarah L Sammons^{1

2

3}, Thibaut Sanglier⁴, Jose Pablo Leone^{1

2

3}, Timothy K Erick^{1

2}, Peter Lambert⁵, Filippo Montemurro⁴, Raf Poppe⁴, Eleonora Restuccia⁴, Sara M Tolaney^{1

2

3}, Nancy U Lin^{1

2

3}

Affiliations

¹ Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
² Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.
³ Harvard Medical School, Boston, MA, USA.
⁴ F. Hoffman-La Roche Ltd, Basel, Basel-Stadt, Switzerland.
⁵ Genentech, Inc, South San Francisco, CA, USA.

PMID: 40163696
DOI: 10.1093/jnci/djaf048

Abstract

Importance: Brain metastases portend poor prognosis in patients with metastatic breast cancer (MBC). Designing treatment and prevention clinical trials requires knowledge of brain metastases incidence with each line of therapy.

Objectives: We assessed the prevalence and cumulative incidence of brain metastases in a large MBC patient cohort by subtype and line of therapy, and the impact of HER2-low expression on prevalence.

Design, setting and outcomes: We analyzed brain metastases prevalence in patients with MBC in a nationwide electronic health record-derived de-identified database. The primary outcome was first diagnosis of brain metastases. We estimated prevalence and incidence of brain metastases by MBC subtype, including HER2-low and therapy line. We used the cumulative incidence function to estimate brain metastases risk in patients without brain metastases at initiation of systemic therapy. All p-values are two-sided, and a p-value ≤ 0.05 indicates statistical significance.

Results: Among 18,075 patients with MBC, 1,102 (6.1%) had at least one brain metastasis at first-line therapy initiation. For the remaining 16,973 patients, cumulative incidence of brain metastases at 60 months was 10% in patients with hormone receptor-positive (HR+)/HER2- disease, 23% for HR+/HER2+ disease, 34% for HR-/HER2+ disease, and 22% for triple-negative breast cancer (TNBC). HER2-low expression within HR+/HER2- and TNBC subtypes had no impact on brain metastases incidence. Brain metastases prevalence increased per line of therapy for patients with all breast cancer subtypes.

Conclusions: Brain metastases incidence increases per line of therapy for every MBC subtype. The HER2-low biomarker does not impact brain metastases incidence within historical subtypes.

Keywords: HER2 low line of therapy; brain metastases; metastatic breast cancer; prevalence.

© The Author(s) 2025. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.