Lipid and Metabolite Deregulation in the Breast Tissue of Women Carrying BRCA1 and BRCA2 Genetic Mutations.
OBJECTIVE
To use localized correlated spectroscopy (COSY) to assess for an altered biochemical state or states in breast tissue of women with BRCA gene mutations that potentially constitute preinvasive conditions.


METHODS
Institutional review board approval was obtained. Participants provided written informed consent. In vivo localized COSY images were recorded at 3 T in the breast tissue of women carrying BRCA1 (n = 9) or BRCA2 (n = 14) gene mutations and were compared with images in healthy control subjects with no family history of breast cancer (n = 10). All participants underwent contrast material-enhanced MR imaging and ultrasonography (US). Statistical significance was calculated with the Mann-Whitney two-sided nonparametric test.


RESULTS
No abnormality was recorded with MR imaging or US. Metabolite levels in the BRCA1 cohort were reduced by 79% (P = .014) when compared with triglycerides level, and there was a 19% increase in lipid unsaturation and triglyceride levels (P = .027 and P = .086, respectively) when compared with cellular cholesterol level. Cholesterol level was reduced by 47% (P = .027) when compared with diallylic lipid level. Metabolite levels in the BRCA2 cohort showed increased unsaturation of 21% (P = .030) relative to triglycerides level. Comparison of the BRCA1 and BRCA2 cohorts showed a 47% (P = .002) increase in cholesterol level in the BRCA2 cohort when compared with diallylic lipid level and a 52% (P = .003) increase when compared with triglycerides level. Levels of diallylic lipid, unsaturated lipid, triglycerides, and terminal methyl on the acyl chain are reduced by 46% (P = .002), 57% (P = .003), 66% (P = .003), and 29% (P = .010), respectively, when compared with cholesterol level.


CONCLUSIONS
Localized COSY recorded significant changes in women with BRCA1 and BRCA2 gene mutations when compared with control subjects. If these changes are ultimately proven to be a premalignant stage, this method may prove useful in screening.
From the Centre for MR in Health, School of Health Sciences, University of Newcastle, Newcastle, NSW, Australia (S.R., G.S., J.B., M.R., D.C., P.M., C.M.); Department of Radiology, Calvary Mater Hospital, Newcastle, NSW, Australia (J.A., K.M.L., P.L.); The Breast and Endocrine Centre, Gateshead, NSW, Australia (J.S., D.C.); and Center for Clinical Spectroscopy, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass (C.M.).
Saadallah
S
Ramadan
Jameen
J
Arm
Judith
J
Silcock
Gorane
G
Santamaria
Jessica
J
Buck
Michele
M
Roy
Kin Men
KM
Leong
Peter
P
Lau
David
D
Clark
Peter
P
Malycha
Carolyn
C
Mountford
D000328:Adult; D001940:Breast / Q000378:metabolism* / Q000503:physiopathology*; D005260:Female; D019398:Genes, BRCA1 / Q000502:physiology*; D024522:Genes, BRCA2 / Q000502:physiology*; D006801:Humans; D050356:Lipid Metabolism; D008875:Middle Aged; D009154:Mutation; D013057:Spectrum Analysis