MR Spectroscopy Shows Early Warning Signs for Women with BRCA

Localized correlated spectroscopy (COSY) recorded significant changes in women with BRCA1 and BRCA2 gene mutations and these findings may prove useful in breast cancer screening, according to a study published in the journal Radiology.

Researchers from Australia and the U.S. performed a study to assess for an altered biochemical state or states in breast tissue in women with BRCA gene mutations that potentially constitute preinvasive conditions.

Nine women, aged 41 to 62, who had genetically confirmed BRCA1 mutation, 14 women, aged 25 to 70, with genetically confirmed BRCA2 mutation, and 10 healthy controls with no family history of breast cancer participated in the study. Five women with BRCA1 mutations and four with BRCA2 mutations had had cysts or lesions.

All participants underwent contrast material–enhanced MR imaging and US. In vivo localized COSY images were recorded at 3 T in the breast tissue of the 23 women. These images were compared with images from the control subjects.

The researchers found no abnormalities recorded with MR imaging or US. However, there were statistically significant differences in the biochemical findings. For the BRCA1 cohort, results showed:

• Metabolite levels in the BRCA1 cohort were reduced by 79% when compared with triglycerides level

• There was a 19% increase in lipid unsaturation and triglyceride levels when compared with cellular cholesterol level

• Cholesterol level was reduced by 47% when compared with diallylic lipid level

Results for the BRCA2 cohort found that metabolite levels showed increased unsaturation of 21% relative to triglycerides level.[[{"type":"media","view_mode":"media_crop","fid":"32647","attributes":{"alt":"Image courtesy of Radiology. ©RSNA, 2015","class":"media-image media-image-right","id":"media_crop_765856427000","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"3445","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 195px; width: 299px; border-width: 0px; border-style: solid; margin: 1px; float: right;","title":"Unenhanced image shows region of interest placement in a 30-year-old control subject. This is the spectroscopic voxel location from which 2D localized COSY data were collected. The experimental conditions were as described previously. Image courtesy of Radiology. ©RSNA, 2015.","typeof":"foaf:Image"}}]]

“Comparison of the BRCA1 and BRCA2 cohorts showed a 47 % increase in cholesterol level in the BRCA2 cohort when compared with diallylic lipid level and a 52% increase when compared with triglycerides level,” the authors wrote.

Reductions, when compared with cholesterol, were also found in:

• Diallylic lipid (46%)

• Unsaturated lipid (57%)

• Triglycerides (66%)

• Terminal methyl on the acyl chain (29%)

“These changes appear to represent a series of early warning signs that may allow women to make informed decisions as to when and if they have prophylactic mastectomy,” coauthor Carolyn Mountford, MSc, DPhil, of the University of Newcastle in Callaghan, Australia, Brigham and Women’s Hospital in Boston, and the Translational Research Institute in Brisbane, said in a release.

“We think there are three stages of pre-cancer progression in the breast tissue," co-author David Clark, MBBS, BSc, FRACS, of the Breast and Endocrine Centre in Gateshead, New South Wales, Australia, added. “Women at Stage 1 could monitor their breasts with follow-up spectroscopy every six months.”

The researchers concluded that localized COSY recorded significant changes in women with BRCA1 and BRCA2 gene mutations when compared with control subjects and if these changes could be proven to be a premalignant stage, this could be a useful, new screening method for breast cancer.