PurposeMetabolomics is the comprehensive global study of metabolites in biological samples. In this retrospective pilot study we explored whether serum metabolomic profile can discriminate the presence of human breast cancer irrespective of the cancer subtype.MethodsPlasma samples were analyzed from healthy women (n = 20) and patients with breast cancer after diagnosis (n = 91) using a liquid chromatography-mass spectrometry platform. Multivariate statistics and a Random Forest (RF) classifier were used to create a metabolomics panel for the diagnosis of human breast cancer.ResultsMetabolomics correctly distinguished between breast cancer patients and healthy control subjects. In the RF supervised class prediction analysis comparing breast cancer and healthy control groups, RF accurately classified 100% both samples of the breast cancer patients and healthy controls. So, the class error for both group in and the out-of-bag error were 0. We also found 1269 metabolites with different concentration in plasma from healthy controls and cancer patients; and basing on exact mass, retention time and isotopic distribution we identified 35 metabolites. These metabolites mostly support cell growth by providing energy and building stones for the synthesis of essential biomolecules, and function as signal transduction molecules. The collective results of RF, significance testing, and false discovery rate analysis identified several metabolites that were strongly associated with breast cancer.ConclusionsIn breast cancer a metabolomics signature of cancer exists and can be detected in patient plasma irrespectively of the breast cancer type.

Hypothesis. Renin-angiotensin system (RAS) has been considered not only as a regulator of systemic volume and electrolyte balance but also has been recently involved in various pathological processes such as cancer. In the etiology of breast cancer, dietary factors have been analyzed and especially the influence of dietary fat has been studied, but the underlying mechanisms remain unclear. In this study, we analyzed RAS-regulating enzymes in serum of rats with N-methyl nitrosourea (NMU)-induced breast cancer fed with different diets. Study Design. Four groups of rats were injected intraperitoneally with 3 doses of 50 mg/kg body weight of NMU at different days after birth and were fed with an AIN-93 commercial diet or AIN-93 diets with 4% fat constituted respectively by extra virgin olive oil, refined sunflower oil, and refined sunflower oil enriched to 50% with oleic acid. Method. After sacrifice, blood and tumor samples were collected by spectrophotometric determinations of RAS-regulating enzymes in plasma and histopathology studies. Results. We show that the type of dietary fat does not influence latency period, incidence of animals with tumors, incidence of mortality, or tumor yield per rat. However, changes were observed in tumor volume and the histopathology. The type of dietary fat also differently modified the enzymes involved in RAS regulation. Conclusions. It might suggest that one of the mechanisms by which dietary fat affects breast cancer is the modification of the RAS system, which may be consider as a new target for integrative therapies.

Amino acid levels are tightly regulated through a continuous cycle of protein formation/degradation to maintain neutral protein balance. Tumor cells require a greater amount of amino acids for the synthesis of new proteins and nucleic acids; therefore, changes in the circulating amino acid profile may be detected and could be used to establish a specific profile for each type of cancer. However, the influence of dietary compounds, which could alter these patterns, has been described in cancer.Here we analyzed the effects of several dietary fats [extra virgin olive oil, sunflower oil and sunflower oil enriched with oleic acid] together with standard commercial diet, on serum free amino acids in rats with N-methyl-nitrosourea-induced breast cancer. We examined the changes in circulating free amino acid levels, as well as if a specific amino acid profile existed and whether the type of dietary fat modified this profile. We found changes in several amino acids, including aspartic acid, glutamine, glycine, 1-methyl-histidine, 3-methyl-histidine, ornithine, taurine and alanine, depending on the type of dietary fat used. Our results indicate that the establishment of a specific amino acid profile for breast cancer could be influenced by external factors such as dietary fat.

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