title: Lipoprotein subfractions by nuclear magnetic resonance are associated with tumor characteristics in breast cancer.
abstract: BACKGROUND
  High-Density Lipoprotein (HDL)-cholesterol, has been associated with breast cancer development, but the association is under debate, and whether lipoprotein subfractions is associated with breast tumor characteristics remains unclear.
  
  
  METHODS
  Among 56 women with newly diagnosed invasive breast cancer stage I/II, aged 35-75 years, pre-surgery overnight fasting serum concentrations of lipids were assessed, and body mass index (BMI) was measured. All breast tumors were immunohistochemically examined in the surgical specimen. Serum metabolomics of lipoprotein subfractions and their contents of cholesterol, free cholesterol, phospholipids, apolipoprotein-A1 and apolipoprotein-A2, were assessed using nuclear magnetic resonance. Principal component analysis, partial least square analysis, and uni- and multivariable linear regression models were used to study whether lipoprotein subfractions were associated with breast cancer tumor characteristics.
  
  
  RESULTS
  The breast cancer patients had following means: age at diagnosis: 55.1 years; BMI: 25.1 kg/m(2); total-Cholesterol: 5.74 mmol/L; HDL-Cholesterol: 1.78 mmol/L; Low-Density Lipoprotein (LDL)-Cholesterol: 3.45 mmol/L; triglycerides: 1.18 mmol/L. The mean tumor size was 16.4 mm, and the mean Ki67 hotspot index was 26.5%. Most (93%) of the patients had estrogen receptor (ER) positive tumors (≥ 1% ER+), and 82% had progesterone receptor (PgR) positive tumors (≥ 10% PgR+). Several HDL subfraction contents were strongly associated with PgR expression: Apolipoprotein-A1 (β 0.46, CI 0.22-0.69, p < 0.001), HDL cholesterol (β 0.95, CI 0.51-1.39, p < 0.001), HDL free cholesterol (β 2.88, CI 1.28-4.48, p = 0.001), HDL phospholipids (β 0.70, CI 0.36-1.04, p < 0.001). Similar results were observed for the subfractions of HDL1-3. We observed inverse associations between HDL phospholipids and Ki67 (β -0.25, p = 0.008), and in particular between HDL1's contents of cholesterol, phospholipids, apolipoprotein-A1, apolipoprotein-A2 and Ki67. No association was observed between lipoproteins and ER expression.
  
  
  CONCLUSIONS
  Our findings hypothesize associations between different lipoprotein subfractions, and PgR expression, and Ki 67 % in breast tumors. These findings may have clinical implications, but require confirmation in larger studies.
authors.affiliation: The Cancer Centre, Oslo University Hospital HF, N-0424, Oslo, Norway. v.g.flote@medisin.uio.no.
authors.forename: Vidar G
authors.identifier: http://orcid.org/0000-0003-2107-0692
authors.initials: VG
authors.lastname: Flote
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Riyas
authors.initials: R
authors.lastname: Vettukattil
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Tone F
authors.initials: TF
authors.lastname: Bathen
authors.affiliation: Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, N-1432, Aas, Norway.
authors.forename: Thore
authors.initials: T
authors.lastname: Egeland
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: McTiernan
authors.affiliation: The Cancer Centre, Oslo University Hospital HF, N-0424, Oslo, Norway.
authors.forename: Hanne
authors.initials: H
authors.lastname: Frydenberg
authors.affiliation: The Cancer Centre, Oslo University Hospital HF, N-0424, Oslo, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Husøy
authors.affiliation: Norwegian Directorate of Health, PO Box 7000, St. Olavs plass, N-0130, Oslo, Norway.
authors.forename: Sissi E
authors.initials: SE
authors.lastname: Finstad
authors.affiliation: Department of Pathology, Oslo University Hospital, N-0424, Oslo, Norway.
authors.forename: Jon
authors.initials: J
authors.lastname: Lømo
authors.affiliation: Department of Pathology, Oslo University Hospital, N-0424, Oslo, Norway.
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Garred
authors.affiliation: Department of Breast and Endocrine Surgery, Oslo University Hospital, N-0424, Oslo, Norway.
authors.forename: Ellen
authors.initials: E
authors.lastname: Schlichting
authors.affiliation: The Cancer Centre, Oslo University Hospital HF, N-0424, Oslo, Norway.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Wist
authors.affiliation: The Cancer Centre, Oslo University Hospital HF, N-0424, Oslo, Norway.|Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, N-9037, Tromsø, Norway.
authors.forename: Inger
authors.initials: I
authors.lastname: Thune
mesh_terms: D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood; D016633:Apolipoprotein A-II / Q000097:blood; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008875:Middle Aged; D025341:Principal Component Analysis; D014280:Triglycerides / Q000097:blood
chemical_list: C505693:APOA1 protein, human; C115794:APOA2 protein, human; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D008076:Cholesterol, HDL; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol
keywords: Breast cancer; HDL; Ki67; Lipoproteins; Progesterone receptor; Subfractions; Tumor