title: Molecular subtype is determinant on inflammatory status and immunological profile from invasive breast cancer patients.
abstract: Breast cancer consists in a chronic inflammatory disease with multiple biological and clinical behaviors. Based on high throughput technologies data, this disease is currently classified according to the molecular expression of estrogen (ER), progesterone (PR) and human epidermal growth factor (HER-2) receptors. In this study, we defined the inflammatory profile of the main molecular subtypes of breast cancer patients: luminal (ER and PR positive, HER-2 negative), HER-2 enriched (HER-2 positive) and triple negative (ER, PR and HER-2 negative). Cytokines panel was assessed by measurement of TNF-α, TGF-β, IL-1, IL-10 and IL-12 plasmatic levels. Oxidative profile was assessed by determination of lipid peroxidation, total antioxidant capacity of plasma, malondialdehyde levels, carbonyl content and nitric oxide (NO). Clinical data were correlated with inflammatory findings. Our findings demonstrated that patients bearing the luminal subtype displayed high TNF-α, TGF-β and enhanced oxidative stress levels associated with reduced IL-12. HER-2-enriched group exhibited higher levels of TNF-α, IL-12 and TGF-β associated with enhanced oxidative stress. Triple-negative subtype exhibited the most aggressive profile of disease behavior, with reduction in both TNF-α and TGF-β, with high levels of lipid peroxidation and NO. The clinical importance of our findings lies in the fact that the inflammatory status varies in distinct ways due to molecular subtype of breast cancer, opening potential therapeutic targets to future therapies.
authors.affiliation: Laboratory of Pathophysiology and Free Radicals, Department of General Pathology, Center of Biological Sciences, State University of Londrina, Londrina, 86051-990, Brazil.
authors.forename: A C S A
authors.initials: AC
authors.lastname: Herrera
authors.forename: C
authors.initials: C
authors.lastname: Panis
authors.forename: V J
authors.initials: VJ
authors.lastname: Victorino
authors.forename: F C
authors.initials: FC
authors.lastname: Campos
authors.forename: A N
authors.initials: AN
authors.lastname: Colado-Simão
authors.forename: A L
authors.initials: AL
authors.lastname: Cecchini
authors.forename: R
authors.initials: R
authors.lastname: Cecchini
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000032:analysis; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D016207:Cytokines / Q000097:blood; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000473:pathology*; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress; D017239:Paclitaxel / Q000627:therapeutic use; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D016207:Cytokines; D004317:Doxorubicin; D008315:Malondialdehyde; D009569:Nitric Oxide; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human