Table 1.

Changes in metabolomics profile of breast cancer.

Study Subject	Comparison Within	Metabolomics Technique Used	Change in Metabolites (Pathways)	References
Breast cancer tissue specimen from African-American Women	Metabolites change in ER + ve versus TNBC tissue specimen	GC-MS LC-MS	Glycolysis, glycogenolysis, TCA cylcle, proliferation and redox pathways metabolites, e.g., NAD+ synthesis pathway; increase in intermediates of transmethylation were increased in TNBC compared to ER + ve.	[54]
267 Human Breast Tissue	Lipid metabolite was compared between breast cancer and normal breast tissue.	UPLC-MS/MS	Membrane phospholipids (phosphatidylcholine, phosphatidylethanolamine, and sphingomyelins ceramides) were increased in breast cancer tissue sample (more in ER-ve samples) than normal breast tissue.	[89]
Breast Cancer tissue from DUKE University Medical center	ER+ve versus ER-ve tumor	GC-MS LC-MS	Glycolytic and glycogenolytic intermediates; glutathione pathway intermediates; onco-metabolites 2-hydroxyglutrate; tryptophan metabolite Kynurenine were elevated in ER-ve tumor compared to ER +ve.	[118]
Serum sample from breast cancer patient	Change in metabolites between obese versus non-obese breast cancer patients	LC-MS	Lipid, carbohydrate, amino acid metabolism metabolites; oxidative phosphorylation, uric acid, ammonia recycling vitamin metabolism (all having role in ATP generation) are increased significantly in obese compared to non-obese breast cancer serum sample. Neurotransmitter metabolites such as serotonin, histamine; acetylcholine is also increased in obese compared to non-obese breast cancer patient serum	[119]
Plasma sample from healthy and breast cancer patient	Breast cancer patient verus healthy control	LC-MS	Increase in antioxidative metabolites (taurine and uric acid); increase in metabolites for bioenergetics (fatty acids capric acid, myristic acid); increase in three branched-chain amino acid which provides carbon for gluconeogenesis (2-hydroxy-3-methylbutiric acid, 2-hydroxy-3-methylpentanoic acid, and 3-methylglutaric acid); increase in nucleic acid biosynthesis substrate (cystidine and inosine diphosphate) in breast cancer patients plasma compared to healthy controls.	[120]
Blood (plasma) sample from healthy and breast cancer patient after overnight fasting	Plasma Metabolomics comparison carried out between breast cancer versus healthy individual	LC-MS	Arginine proline metabolism pathway metabolites and tryptophan metabolism pathway metabolites decreased and fatty acid biosynthesis pathway metabolites increases in plasma of breast cancer when compared to normal healthy individual.	[121]
Breast cancer patient tissue specimen	Comparison was made between metabolites in different sub-group of luminal A (A1, A2 and A3)	HR MAS MRS (High resolution magic angle spinning magnetic resonance spectroscopy)	Glucose signal was lower in A2 compared to A1 and A3. α-hydrogen amino acid signal was lower in A1 higher in A3 compared to A2. Al anine signal was higher in A2 compared to A3. Myo-inositol signal was lower in A1 than A2 and A3.	[122]
Breast cancer cell line MCF-7S (Adriamycin-sensitive) and MCF-7Adr (Adriamycin-resistant)	Effect of Adriamycin in metabolic profile of MCF-7S and MCF-7Adr Cell lines	GC-MS	Adriamycin significantly increases the metabolite as glucose, glutamine; amino acids such as valine isoleucine serine threonine, etc., while adriamycin slightly changed metabolites such as serine isoleucine glutamic acid after long-term exposure.	[123]
Serum sample from breast cancer patient	Comparing the metabolites in full response/pCR (pathological complete response), partial response (PR) and no response/SD (stable disease) to neoadjuvant chemotherapy	NMR LC-MS	Four metabolites were detected with threonine and glutamine decreased in pCR group compared to SD group. Isoleucine increased in pCR group compared to SD and PR and linolenic acid was decreased in pCR group and increased in both PR and SD group.	[124]
Fasting blood (serum and plasma) sample from healthy and breast cancer patients		LC-TOF-MS (Liquid chromatography time of flight mass spectrometry) GC-TOFMS (Gas chromatography time of flight mass spectrometry)	Taurine pathway metabolite (hypotaurine, pyruvate); pyruvate the metabolite for glycine, serine threonine metabolism is increased in breast cancer than in normal healthy individual. While amino acid like succinate, choline, serine, glycine and alanine and glycerol 3 phosphate, metabolite in phospholipid biosynthesis are decreased in both plasma and serum sample of breast cancer patient when compared to normal healthy individual.	[125]