Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2021 Jun 1;23(6):894-904.
doi: 10.1093/neuonc/noaa285.

The incidence of brain metastases among patients with metastatic breast cancer: a systematic review and meta-analysis

Markus Kuksis  1 , Yizhuo Gao  2 , William Tran  3   4 , Christianne Hoey  3 , Alex Kiss  3 , Adam S Komorowski  5 , Aman J Dhaliwal  2 , Arjun Sahgal  3   4 , Sunit Das  6 , Kelvin K Chan  7   8 , Katarzyna J Jerzak  3   7
Affiliations
Meta-Analysis

The incidence of brain metastases among patients with metastatic breast cancer: a systematic review and meta-analysis

Markus Kuksis et al. Neuro Oncol. .

Abstract

Background: Patients with metastatic breast cancer (MBC) are living longer, but the development of brain metastases often limits their survival. We conducted a systematic review and meta-analysis to determine the incidence of brain metastases in this patient population.

Methods: Articles published from January 2000 to January 2020 were compiled from four databases using search terms related to breast cancer, brain metastasis, and incidence. The overall and per patient-year incidence of brain metastases were extracted from studies including patients with human epidermal growth factor receptor-2 positive (HER2+), triple negative, and hormone receptor (HR)+/hormone receptor negative (HER2-) MBC; pooled overall estimates for incidence were calculated using random effects models.

Results: 937 articles were compiled, and 25 were included in the meta-analysis. Incidence of brain metastases in patients with HER2+ MBC, triple negative MBC, and HR+/HER2- MBC was reported in 17, 6, and 4 studies, respectively. The pooled cumulative incidence of brain metastases was 31% for the HER2+ subgroup (median follow-up: 30.7 months, IQR: 24.0-34.0), 32% for the triple negative subgroup (median follow-up: 32.8 months, IQR: 18.5-40.6), and 15% among patients with HR+/HER2- MBC (median follow-up: 33.0 months, IQR: 31.9-36.2). The corresponding incidences per patient-year were 0.13 (95% CI: 0.10-0.16) for the HER2+ subgroup, 0.13 (95%CI: 0.09-0.20) for the triple negative subgroup, and only 0.05 (95%CI: 0.03-0.08) for patients with HR+/HER2- MBC.

Conclusion: There is a high incidence of brain metastases among patients with HER2+ and triple negative MBC. The utility of a brain metastases screening program warrants investigation in these populations.

Keywords: brain metastases; human epidermal growth factor receptor-2 positive (HER2+); incidence; metastatic breast cancer; triple negative.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Schematic illustrating study selection process. Adapted from PRISMA flow diagram 2009. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Fig. 2
Fig. 2
A) Forest plot of pooled incidence rate (patient-years) for HER2+ MBC. Random effects model presented. Incidence per year of follow-up ranged from 0.04 to 0.27. Median follow-up times ranged from 5.8 to 53.6 months. B) Funnel Plot for publication bias according to studies reporting brain metastasis in HER2+ MBC. Egger’s test; P = 0.30. HER2+, human epidermal growth factor receptor-2 positive; MBC, metastatic breast cancer.
Fig. 3
Fig. 3
A) Forest plot of pooled incidence rate (patient-years) for HR+/HER2− MBC. Random effects model presented. Incidence per year of follow-up ranged from 0.03–0.10. Median follow-up times ranged from 32.0–42.8 months. B) Funnel plot for publication bias according to studies reporting brain metastasis in HR+/HER2− MBC. HER2−, hormone receptor negative; HR+, hormone receptor; MBC, metastatic breast cancer.
Fig. 4
Fig. 4
A) Forest plot of pooled incidence rate (patient-years) for triple negative MBC. Random effects model presented. Incidence per year of follow-up ranged from 0.07 to 0.31. Median follow-up times ranged from 12.0 to 48.1 months. B) Funnel plot illustrating studies reporting brain metastasis in triple negative MBC. MBC, metastatic breast cancer.
Fig. 5
Fig. 5
A) Forest plot of pooled incidence rate (patient-years) for MBC, irrespective of subtype. Random effects model presented. Incidence per year of follow-up ranged from 0.02 to 0.19. Median follow-up times ranged from 12.0 to 137.0 months. B) Funnel Plot for publication bias according to studies reporting brain metastasis in MBC, irrespective of subtype. Egger’s test, P = 0.88. MBC, metastatic breast cancer.
See this image and copyright information in PMC

Comment in

  • Letter to the editor concerning Kuksis et al.
    Schwartz NRM, Dalmat RR. Schwartz NRM, et al. Neuro Oncol. 2021 Aug 2;23(8):1404-1405. doi: 10.1093/neuonc/noab050. Neuro Oncol. 2021. PMID: 33982751 Free PMC article. No abstract available.
  • Reply to letter by Schwartz et al.
    Kuksis M, Gao Y, Kiss A, Jerzak KJ. Kuksis M, et al. Neuro Oncol. 2021 Aug 2;23(8):1406-1407. doi: 10.1093/neuonc/noab078. Neuro Oncol. 2021. PMID: 33982755 Free PMC article. No abstract available.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Gori S, Rimondini S, De Angelis V, et al. . Central nervous system metastases in HER-2 positive metastatic breast cancer patients treated with trastuzumab: incidence, survival, and risk factors. Oncologist. 2007;12(7):766–773. - PubMed
    1. Clayton AJ, Danson S, Jolly S, et al. . Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer. Br J Cancer. 2004;91(4):639–643. - PMC - PubMed
    1. Brufsky AM, Mayer M, Rugo HS, et al. . Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER. Clin Cancer Res. 2011;17(14):4834–4843. - PubMed
    1. Lin NU, Claus E, Sohl J, Razzak AR, Arnaout A, Winer EP. Sites of distant recurrence and clinical outcomes in patients with metastatic triple-negative breast cancer: high incidence of central nervous system metastases. Cancer. 2008;113(10):2638–2645. - PMC - PubMed
    1. Shmueli E, Wigler N, Inbar M. Central nervous system progression among patients with metastatic breast cancer responding to trastuzumab treatment. Eur J Cancer. 2004;40(3):379–382. - PubMed

Substances

  NODES
twitter 2