How Does Breast Cancer Heterogeneity Determine Changes in Tumor Marker Levels in Saliva?

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.