Saliva is a promising biological fluid for the diagnosis and monitoring of diseases, including breast cancer. To study the composition of saliva, a complex of “omics” technologies is used: genomics, transcriptomics, proteomics, metabolomics and microbiomics. In this review, we systematized all known “omics” in their application to saliva analysis in breast cancer in order to understand how complete the picture is provided by the combination of different areas of research and to identify missing links. It has been shown that studies of saliva in breast cancer are chaotic and unsystematic. Inconsistency of sample sizes and high heterogeneity of breast cancer were identified. The main tasks that need to be solved for the complete and harmonious development of salivaomics in a new direction—“salivaonkoomics” are formulated. Thus, it is necessary to systematize and unify the study of biomarkers within each area of “omics”, including sample size and its homogeneity, a list of methods and approaches, a list of biomarkers, reproducibility of results, and the ability to transfer results to other samples. It is important to expand the number of components of “omics” by adding new methods (for example, spectralomics, etc.), as well as studying the relationships between different “omics” technologies (interactomics). All this together will allow the study of saliva not only in breast cancer but also in many other pathologies to a qualitatively new level.

The MUC1 family of transmembrane glycoproteins (CA 15-3, CA 27.29, MCA) is aberrantly expressed among patients with breast cancer. Objectives: to measure the level of degradation products of MUC1, including CA 15-3, CA 27.29, and MCA, in the saliva of breast cancer patients and to describe the biochemical processes that influence their expression and the regulation of their biological functions. Methods: The case–control study included three groups (breast cancer, fibroadenomas, and healthy controls). All study participants provided saliva samples strictly before starting treatment. The levels of MUC1, including CA 15-3, CA 27.29, and MCA, free progesterone and estradiol, cytokines (MCP-1, VEGF, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18), and amino acids (Asp, Gln, Gly, His, Leu + Ile, Orn, Phe, Pro, Tyr) were determined. Results: It was shown that the levels of the MUC1 family in the saliva of patients with HER2-positive breast cancer were significantly lower compared to the control group. The level of pro-inflammatory cytokines and the level of free estradiol affected the expression of MUC1. We obtained a reliable relationship between the aggressive nature of tumor growth, an increased level of pro-inflammatory cytokines, a low level of free estradiol, and the suppressed expression of salivary MUC1. Conclusions: Among patients with aggressive breast cancer, a high level of pro-inflammatory cytokines, and a low level of free estradiol, there was an inhibition of the expression of pathologically unchanged glycoprotein MUC1 in saliva.

Amino acid metabolism in breast cancer cells is unique for each molecular biological subtype of breast cancer. In this review, the features of breast cancer cell metabolism are considered in terms of changes in the amino acid composition due to the activity of transmembrane amino acid transporters. In addition to the main signaling pathway PI3K/Akt/mTOR, the activity of the oncogene c-Myc, HIF, p53, GATA2, NF-kB and MAT2A have a direct effect on the amino acid metabolism of cancer cells, their growth and proliferation, as well as the maintenance of homeostatic equilibrium. A distinctive feature of luminal subtypes of breast cancer from TNBC is the ability to perform gluconeogenesis. Breast cancers with a positive expression of the HER2 receptor, in contrast to TNBC and luminal A subtype, have a distinctive active synthesis and consumption of fatty acids. It is interesting to note that amino acid transporters exhibit their activity depending on the pH level inside the cell. In the most aggressive forms of breast cancer or with the gradual progression of the disease, pH will also change, which will directly affect the metabolism of amino acids. Using the cell lines presented in this review, we can trace the characteristic features inherent in each of the molecular biological subtypes of breast cancer and develop the most optimal therapeutic targets.

This study of the features of the biochemical composition of biological fluids in patients with breast cancer, including saliva, allows us to identify some indicators as metabolic predictors of the presence of the disease. Objectives: to study the influence of the menopause factor and body mass index (BMI) on the biochemical composition of saliva and to evaluate the applicability of metabolic markers of saliva for the diagnosis of breast cancer. Methods: The case–control study involved 1438 people (breast cancer, n = 543; fibroadenomas, n = 597; control, n = 298). A comprehensive study of the biochemical composition of saliva was carried out using 36 parameters. Results: When comparing the salivary biochemical composition in breast cancer, fibroadenomas, and controls, it is necessary to take into account the menopausal status, as well as BMI (less than 25 or more) for the group of patients with preserved menstrual function. A complex of biochemical parameters has been identified that change in saliva during breast cancer, regardless of menopause and BMI (total protein, urea, uric acid, NO, α-amino acids, GGT), as well as specific parameters that must be taken into account when analyzing individual subgroups (imidazole compounds, LDH, catalase, α-amylase). During the study of a separate group of patients with leaf-shaped (phyllodes) tumors, we found similarities with breast cancer in the changes in some biochemical parameters that can be attributed to metabolites of malignant growth (protein, α-amino acids, calcium, NO, pyruvate, peroxidase, α-amylase). Conclusions: We demonstrated changes in a wide range of salivary biochemical parameters depending on the presence of fibroadenomas and breast cancer. From the point of view of clinical practice, this may be useful information for monitoring the condition of patients with fibroadenomas, which are difficult to unambiguously classify based on instrumental diagnostics alone.

Changes in the concentration of tryptophan (Trp) indicate a serious metabolic restructuring, which is both a cause and a consequence of many diseases. This work examines the upward change in salivary Trp concentrations among patients with breast cancer. This study involved volunteers divided into three groups: breast cancer (n = 104), non-malignant breast pathologies (n = 30) and healthy controls (n = 20). In all participants, before treatment, the quantitative content of Trp in saliva was determined by capillary electrophoresis. In 20 patients with breast cancer, Trp was re-tested four weeks after surgical removal of the tumor. An increase in the Trp content in saliva in breast cancer has been shown, which statistically significantly decreases after surgical removal of the tumor. A direct correlation was found between increased Trp levels with the degree of malignancy and aggressive molecular subtypes of breast cancer, namely triple negative and luminal B-like HER2-negative. These conclusions were based on an increase in Ki-67 and an increase in Trp in HER2-negative and progesterone-negative subtypes. Factors under which an increase in Trp concentration in saliva was observed were identified: advanced stage of breast cancer, the presence of regional metastasis, low tumor differentiation, a lack of expression of HER2, estrogen and progesterone receptors and the high proliferative activity of the tumor. Thus, the determination of salivary Trp may be a valuable tool in the study of metabolic changes associated with cancer, particularly breast cancer.

High heterogeneity of breast cancer is due to a large variety of cancer cell characteristics at the genomic, epigenomic, transcriptome, and proteomic levels. One of the difficulties is the separation of molecular biological subtypes based on the expression of tumor markers. Another problem is the difficulty of venipuncture in cancer patients when taking blood at different stages of patient care. Objectives: To identify statistically significant changes in the level of salivary tumor markers depending on the molecular biological subtype of breast cancer in order to improve understanding of the individual properties of each of its subtypes, 140 volunteers (breast cancer—110; healthy control—30) took part in the case–control study. Saliva was collected strictly before the start of treatment, and the content of ten tumor markers was determined by ELISA: EGFR2, CA15-3, CA27.29, MCA, CEA, CA125, CA19-9, CYFRA 21-1, ferritin, and CRP. The content of MUC1 antigens (CA15-3, CA27.29, and MCA) statistically significantly decreased in the luminal B(+) subtype of breast cancer. The CA19-9 antigen showed high sensitivity to low HER2 expression. A reliable increase in the level of CYFRA 21-1 in saliva was shown in luminal A and luminal B(-) breast cancer. The work demonstrates the diagnostic capabilities of saliva in measuring tumor markers in patients with breast cancer. It was also found that there are reliable differences in the expression level and set of tumor markers in saliva depending on the molecular biological subtype of breast cancer. Thus, CYFRA 21-1 significantly increases with luminal A and luminal B(-), but CRP only increases with luminal A. CA15-3, CA27.29, MCA, and CA19-9 significantly decrease with luminal B(+) breast cancer.