title: A Presurgical Study of Oral Silybin-Phosphatidylcholine in Patients with Early Breast Cancer.
abstract: Silybin-phosphatidylcholine is an orally bioavailable complex of silybin, a polyphenolic flavonolignan derived from milk thistle, endowed with potential anticancer activity in preclinical models. The purpose of this window of opportunity trial was to determine, for the first time in early breast cancer patients, the breast tissue distribution of silybin. Twelve breast cancer patients received silybin-phosphatidylcholine, 2.8 g daily for 4 weeks prior to surgery. Silybin levels were measured before (SIL) and after (TOT-SIL) enzymatic hydrolysis by high-performance liquid chromatography (HPLC)-MS/MS in biologic samples (plasma, urine, breast cancer, and surrounding normal tissue). Fasting blood samples were taken at baseline, before the last administration, and 2 hours later. All patients were fully compliant and completed the treatment program. No toxicity was observed. SIL and TOT-SIL were undetectable in baseline samples. Despite a high between-subject variability, repeated administration of Siliphos achieved levels of TOT-SIL of 31,121 to 7,654 ng/mL in the plasma and up to 1,375 ng/g in breast cancer tissue. SIL concentrations ranged from 10,861 to 1,818 ng/mL in plasma and up to 177 ng/g in breast cancer tissue. Median TOT-SIL concentration was higher in the tumor as compared with the adjacent normal tissue (P = 0.018). No significant change in either blood levels of IGF-I and nitric oxide or Ki-67 in tumors was noted. Silybin-phosphatidylcholine, taken orally, can deliver high blood concentrations of silybin, which selectively accumulates in breast tumor tissue. These findings provide the basis for a future phase II biomarker trial in breast cancer prevention.
authors.affiliation: Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy. matteo.lazzeroni@ieo.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Lazzeroni
authors.affiliation: Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy.
authors.forename: Aliana
authors.initials: A
authors.lastname: Guerrieri-Gonzaga
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Gandini
authors.affiliation: Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy.
authors.forename: Harriet
authors.initials: H
authors.lastname: Johansson
authors.affiliation: Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Serrano
authors.affiliation: Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cazzaniga
authors.affiliation: Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Aristarco
authors.affiliation: Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Puccio
authors.affiliation: Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Mora
authors.affiliation: Division of Senology, European Institute of Oncology, Milan, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Caldarella
authors.affiliation: Division of Senology, European Institute of Oncology, Milan, Italy.
authors.forename: Gianmatteo
authors.initials: G
authors.lastname: Pagani
authors.affiliation: Division of Pathology, European Institute of Oncology, Milan, Italy. School of Medicine, University of Milan, Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Pruneri
authors.affiliation: INDENA S.p.A, Milan, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Riva
authors.affiliation: INDENA S.p.A, Milan, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Petrangolini
authors.affiliation: INDENA S.p.A, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Morazzoni
authors.affiliation: Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy. Division of Medical Oncology, E.O. Ospedali Galliera, Genoa, Italy. Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Andrea
authors.initials: A
authors.lastname: DeCensi
authors.affiliation: Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Bonanni
mesh_terms: D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006868:Hydrolysis; D008875:Middle Aged; D010713:Phosphatidylcholines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D010713:Phosphatidylcholines; D012838:Silymarin; D000077385:Silybin