A systematic review of candidate genes and their relevant pathways for metastasis among adults diagnosed with breast cancer.

Background: Presently incurable, metastatic breast cancer is estimated to occur in as many as 30% of those diagnosed with early-stage breast cancer. Timely and accurate identification of those at risk for developing metastasis using validated biomarkers has the potential to have profound impact on overall survival rates. Our primary goal was to conduct a systematic review and synthesize the existing body of scientific knowledge on the candidate genes and their respective single nucleotide polymorphisms associated with metastasis-related outcomes among patients diagnosed with breast cancer. This knowledge is critical to inform future hypothesis-driven and validation research aimed at enhancing clinical decision-making for breast cancer patients.

Methods: Using PRISMA guidelines, literature searches were conducted on September 13th, 2023, using PubMed and Embase databases. The systematic review protocol was registered with INPLASY (DOI: https://doi.org/10.37766/inplasy2024.8.0014 ). Covidence software was used to facilitate the screening and article extraction processes. Peer-reviewed articles were selected if authors reported on single nucleotide polymorphisms directly associated with metastasis among adults diagnosed with breast cancer.

Findings: We identified 451 articles after 44 duplicates were removed resulting in 407 articles to be screened for study inclusion. Three reviewers completed the article screening process which resulted in 86 articles meeting the study inclusion criteria. Sampling varied across studies with the majority utilizing a case-control design (n = 75, 87.2%), with sample sizes ranging from 23 to 1,017 participants having mean age 50.65 ± 4.50 (min-max: 20-75). The synthesis of this internationally generated evidence revealed that the scientific area on the underlying biological contributions to breast cancer metastasis remains predominantly exploratory in nature (n = 74, 86%). Of the 12 studies with reported power analyses, only 9 explicitly stated the power values which ranged from 47.88 to 99%.

Discussion: Understanding the underlying biological mechanisms contributing to metastasis is a critical component for precision oncological therapeutics and treatment approaches. Current evidence investigating the contribution of SNPs to the development of metastasis is characterized by underpowered candidate gene studies. To inform individualized precision health practices and improve breast cancer survival outcomes, future hypothesis-driven research is needed to replicate these associations in larger, more diverse datasets.