Nutritional Metabolomics in Diet–Breast Cancer Relations: Current Research, Challenges, and Future Directions—A Review

Abstract

Breast cancer is one of the most common types of cancer in women worldwide, and its incidence is increasing. Diet has been identified as a modifiable risk factor for breast cancer, but the complex interplay between diet, metabolism, and cancer development is not fully understood. Nutritional metabolomics is a rapidly evolving field that can provide insights into the metabolic changes associated with dietary factors and their impact on breast cancer risk. The review’s objective is to provide a comprehensive overview of the current research on the application of nutritional metabolomics in understanding the relationship between diet and breast cancer. The search strategy involved querying several electronic databases, including PubMed, Scopus, Web of Science, and Google Scholar. The search terms included combinations of relevant keywords such as “nutritional metabolomics”, “diet”, “breast cancer”, “metabolites”, and “biomarkers”. In this review, both in vivo and in vitro studies were included, and we summarize the current state of knowledge on the role of nutritional metabolomics in understanding the diet–breast cancer relationship, including identifying specific metabolites and metabolic pathways associated with breast cancer risk. We also discuss the challenges associated with nutritional metabolomics research, including standardization of analytical methods, interpretation of complex data, and integration of multiple-omics approaches. Finally, we highlight future directions for nutritional metabolomics research in studying diet–breast cancer relations, including investigating the role of gut microbiota and integrating multiple-omics approaches. The application of nutritional metabolomics in the study of diet–breast cancer relations, including 2-amino-4-cyano butanoic acid, piperine, caprate, rosten-3β,17β-diol-monosulfate, and γ-carboxyethyl hydrochroman, among others, holds great promise for advancing our understanding of the role of diet in breast cancer development and identifying personalized dietary recommendations for breast cancer prevention, control, and treatment.

Onco-Breastomics: An Eco-Evo-Devo Holistic Approach

“…Parabens (MP, EP, PP, BP) earlier BC development [135], potent carcinogens [121] mimic of endogenous hormones, interact with signaling transduction pathways, such as HER2 signaling, modulate of key enzymes involved in estrogen metabolism, increase pro-oncogenic c-Myc expression in ER+/HER2+ BC cells, promote EMT [135] BC and non-malignant cell lines [121] RT-qPCR, WB [121] Polychlorinated biphenyls (PCBs) increased BCR [136] as EDC [137], enhance metastatic proprieties of BC cells by activating ROCK, increase cell motility/migration/invasion, disease progression, induce the intracellular ROS production [138] human BC cell lines, animal models [138], mice mammary organoid cultures [125] LC-MS/MS [125] Dioxins and dioxin-like chemicals (TCDD) controversially role: positive association between airborne dioxins and invasive BCR [139]; no increased BCR for long-term airborne dioxins [140]; no association between dietary dioxin and BCR [141]; significant positive association between dioxin exposure and BCR [142]; protective effect against BC [143] disruption of the CXCL12/CXCR4 axis limits the metastasis of BC cells to the lung in mice [143]; BC cells may acquire pro-metastatic and CSCs features [144] BC cell lines [143], co-culture model using MCF7 and MDA-MB-231 BC cell lines together with hMADS preadipocytes and in vivo Zebrafish larvae model [144] gene chip microarray, RT-PCR, FC [143], nLC-MS/MS, qRT-PCR, Zebrafish larva metastasis assays [144] Dietary factors [145] Omics: nutrigenomics and nutriproteomics [102], nutritional epigenomics/epitranscriptomics, and epiproteomics [104], phosphoproteomics [146], metabolomics/nutritional metabolomics [103,145,146] High fructose intake PT [147,148], fructose-induced carcinogenesis…”

“…Sellami et al (2020) showed that nutrigenomics and nutriproteomics are recently developed omics fields that are focused on the interaction between nutrients and human genome/proteome in order to decipher the role of dietary factors in carcinogenesis [102]. Additionally, Vahid et al (2023) revealed that nutritional metabolomics is a rapidly evolving field developed as an interplay between dietary factors, metabolic changes, and breast carcinogenesis or breast cancer risk (BCR) [103]. Nutritional epigenomics/epitranscriptomics/epiproteomics are focused on the influence of nutrients and bioactive dietary components on cytosine methylation, histone PTMs and specific RNA molecules as main epigenetic factors involved in BC development [104].…”

Can a Low-Phosphate Diet for Chronic Kidney Disease Treat Cancer? An Interdisciplinary Literature Review

“…Importantly, metabolomics, the study of chemical metabolites derived from metabolic processes "offers an opportunity to develop a biomarker-based approach to dietary assessment in cancer epidemiology" [21]. A 2023 review of nutritional metabolomics in the association of diet and breast cancer described a wide variety of metabolites from fat, protein, carbohydrate, and other nutrients, but significantly, no mention was made of metabolites related to dietary phosphate [22]. Yet, circulating serum Pi derived from dietary phosphorus absorbed in the intestines "functions as a constituent of cellular metabolites" [23].…”