Genomics of Breast Cancer Brain Metastases: A Meta-Analysis and Therapeutic Implications

Thuy Thi Nguyen; Diaddin Hamdan; Eurydice Angeli; Jean-Paul Feugeas; Quang Van Le; Frédéric Pamoukdjian; Guilhem Bousquet

doi:10.3390/cancers15061728

Genomics of Breast Cancer Brain Metastases: A Meta-Analysis and Therapeutic Implications

Cancers (Basel). 2023 Mar 12;15(6):1728. doi: 10.3390/cancers15061728.

Authors

Thuy Thi Nguyen^{1

2

3

4}, Diaddin Hamdan^{2

5}, Eurydice Angeli^{2

4

6}, Jean-Paul Feugeas^{7

8}, Quang Van Le^{1

2}, Frédéric Pamoukdjian^{2

4

9}, Guilhem Bousquet^{2

4

6}

Affiliations

¹ National Cancer Hospital, Ha Noi 100000, Vietnam.
² Institut National de la Santé Et de la Recherche Médicale (INSERM), Université Paris Cité, UMR_S942 MASCOT, 75006 Paris, France.
³ Department of Pediatrics, Hanoi Medical University, Ha Noi 100000, Vietnam.
⁴ Institut Galilée, Université Sorbonne Paris Nord, 93439 Villetaneuse, France.
⁵ Hôpital La Porte Verte, 78000 Versailles, France.
⁶ Service d'Oncologie Médicale, Hôpital Avicenne, Assistance Publique Hôpitaux de Paris, 93000 Bobigny, France.
⁷ INSERM U1098, 25030 Besançon, France.
⁸ Laboratoire de Biochimie Hôpital Jean Minjoz, Université de Franche-Comté, 25000 Besançon, France.
⁹ Service de Médecine Gériatrique, Hôpital Avicenne, Assistance Publique Hôpitaux de Paris, 93000 Bobigny, France.

Abstract

Breast cancer brain metastases are a challenging daily practice, and the biological link between gene mutations and metastatic spread to the brain remains to be determined. Here, we performed a meta-analysis on genomic data obtained from primary tumors, extracerebral metastases and brain metastases, to identify gene alterations associated with metastatic processes in the brain. Articles with relevant findings were selected using Medline via PubMed, from January 1999 up to February 2022. A critical review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement (PRISMA). Fifty-seven publications were selected for this meta-analysis, including 37,218 patients in all, 11,906 primary tumor samples, 5541 extracerebral metastasis samples, and 1485 brain metastasis samples. We report the overall and sub-group prevalence of gene mutations, including comparisons between primary tumors, extracerebral metastases and brain metastases. In particular, we identified six genes with a higher mutation prevalence in brain metastases than in extracerebral metastases, with a potential role in metastatic processes in the brain: ESR1, ERBB2, EGFR, PTEN, BRCA2 and NOTCH1. We discuss here the therapeutic implications. Our results underline the added value of obtaining biopsies from brain metastases to fully explore their biology, in order to develop personalized treatments.

Keywords: brain metastases; breast cancer; genomics; specific gene panel.

Grants and funding

This meta-analysis was funded by the University Sorbonne Paris Nord International Scholarship, Erasmus+ kit mobility, number KA107. The funder of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.