title: Oxidant stress as a major determinant of platelet activation in invasive breast cancer.
abstract: The hypothesis that increased oxidative stress in breast cancer (BC) patients could induce enhanced lipid peroxidation, which, in turn, would contribute to platelet activation and poor clinical outcome is attractive. To address this issue, we investigated pre-surgical urinary 8-iso-prostaglandin (PG)F2α(marker of in vivo oxidative stress) and 11-dehydro-thromboxane (TX)B2(marker of in vivo platelet activation) levels in patients with primary BC (n = 115) compared with control women paired for comorbidities and their association with patients' metabolic profile and clinical prognostic factors. The results obtained showed that presurgical urinary excretion of both biomarkers was enhanced in BC patients compared to controls and was associated with patients' estrogen receptor (ER) expression, but not HER2 status or Ki67 proliferation index. Accordingly, both urinary biomarkers were increased in patients with luminal-like BC molecular subtypes compared with triple negative or HER2-enriched tumors. ER status was an independent predictor of 8-iso-PGF2αurinary levels, which, in turn, significantly predicted 11-dehydro-TXB2urinary levels together with disease stage and ER status. The prognostic value of 11-dehydro-TXB2was then evaluated showing a significant correlation with BC pathological response to neoadjuvant treatment. Furthermore, among relapsing patients, those with elevated urinary biomarker levels were more likely to develop distant metastasis rather than local recurrence. In conclusion, we may speculate that enhanced oxidative stress due to estrogen-related mechanisms might cause a condition of persistent platelet activation capable of sustaining BC growth and progression through the release of bioactive stored molecules, ultimately contributing to tumor invasiveness. Further studies specifically addressing this hypothesis are presently needed.
authors: San Raffaele Roma Open University, Via di Val Cannuta 247, Rome, 00166, Italy.|Interinstitutional Multidisciplinary BioBank (BioBIM), IRCCS San Raffaele Pisana, Via di Val Cannuta 247, Rome, 00166, Italy.
authors: Patrizia
authors: P
authors: Ferroni
authors: Department of Medicine and Aging, and Center of Aging Science and Translational Medicine (CESI-Met), Via Colle dell'Ara, Chieti, 66013, Italy.
authors: Francesca
authors: F
authors: Santilli
authors: Department of Surgery, San Giovanni Hospital-Addolorata, Via dell'Amba Aradan 9, Rome, 00184, Italy.
authors: Francesco
authors: F
authors: Cavaliere
authors: Department of Medicine and Aging, and Center of Aging Science and Translational Medicine (CESI-Met), Via Colle dell'Ara, Chieti, 66013, Italy.
authors: Paola
authors: P
authors: Simeone
authors: Department of Pathology, San Giovanni Hospital-Addolorata, Via dell'Amba Aradan 9, Rome, 00184, Italy.
authors: Leopoldo
authors: L
authors: Costarelli
authors: Department of Medicine and Aging, and Center of Aging Science and Translational Medicine (CESI-Met), Via Colle dell'Ara, Chieti, 66013, Italy.
authors: Rossella
authors: R
authors: Liani
authors: Department of Medicine and Aging, and Center of Aging Science and Translational Medicine (CESI-Met), Via Colle dell'Ara, Chieti, 66013, Italy.
authors: Romina
authors: R
authors: Tripaldi
authors: Interinstitutional Multidisciplinary BioBank (BioBIM), IRCCS San Raffaele Pisana, Via di Val Cannuta 247, Rome, 00166, Italy.|Department of Systems Medicine, Medical Oncology, Tor Vergata Clinical Center, Tor Vergata University of Rome, Viale Oxford 81, Rome, 00133, Italy.
authors: Silvia
authors: S
authors: Riondino
authors: Department of Systems Medicine, Medical Oncology, Tor Vergata Clinical Center, Tor Vergata University of Rome, Viale Oxford 81, Rome, 00133, Italy.
authors: Mario
authors: M
authors: Roselli
authors: Department of Medicine and Aging, and Center of Aging Science and Translational Medicine (CESI-Met), Via Colle dell'Ara, Chieti, 66013, Italy.
authors: Giovanni
authors: G
authors: Davi
authors: San Raffaele Roma Open University, Via di Val Cannuta 247, Rome, 00166, Italy.|Interinstitutional Multidisciplinary BioBank (BioBIM), IRCCS San Raffaele Pisana, Via di Val Cannuta 247, Rome, 00166, Italy.
authors: Fiorella
authors: F
authors: Guadagni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000652:urine; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology / Q000652:urine; D018384:Oxidative Stress / Q000502:physiology*; D015539:Platelet Activation / Q000502:physiology*; D011960:Receptors, Estrogen / Q000378:metabolism; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; C075750:8-epi-prostaglandin F2alpha; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D015237:Dinoprost
keywords: breast cancer; estrogen receptors; metastasis; oxidative stress; platelet activation