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Genomics of Breast Cancer Brain Metastases: A Meta-Analysis and Therapeutic Implications
Thuy Thi Nguyen1,2,3,4, Diaddin Hamdan2,5, Eurydice Angeli2,4,6
1National Cancer Hospital, Ha Noi 100000, Vietnam.
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.
Insights
This meta-analysis identified six key genes (ESR1, ERBB2, EGFR, PTEN, BRCA2, NOTCH1) with higher mutation prevalence in breast cancer brain metastases. Understanding these gene alterations can guide personalized treatments for brain metastases.
Area of Science:
- Oncology
- Genomics
- Translational Research
Background:
- Breast cancer brain metastases present significant clinical challenges.
- The genetic drivers of brain metastasis remain incompletely understood.
Purpose of the Study:
- To identify gene alterations associated with breast cancer brain metastasis through a comprehensive meta-analysis.
- To compare gene mutation prevalence across primary tumors, extracerebral metastases, and brain metastases.
Main Methods:
- Systematic literature search of Medline via PubMed (1999-2022).
- Meta-analysis of genomic data from 57 publications including 37,218 patients.
- PRISMA guidelines followed for critical review.
Main Results:
- Identified six genes (ESR1, ERBB2, EGFR, PTEN, BRCA2, NOTCH1) with increased mutation frequency in brain metastases compared to extracerebral metastases.
- Reported overall and subgroup prevalence of gene mutations across different metastatic sites.
- Highlighted potential roles of these genes in brain metastatic processes.
Conclusions:
- Genomic analysis of brain metastases provides crucial insights into metastatic biology.
- Targeting identified gene alterations may lead to personalized treatment strategies for breast cancer patients with brain metastases.
