Women with mutations in the BRCA1 or BRCA2 genes have an increased risk of developing breast cancer. While lifetime risk is up to 60% for BRCA1 and 45% for BRCA2, some women develop breast cancer at an early age while other women with the same mutation never develop breast cancer. There is currently no method to predict which women will develop breast cancer nor when they will develop it. As a result, many women undergo a prophylactic mastectomy to mitigate risk. Two dimensional localised Correlated Spectroscopy (2D L-COSY) with a basis from earlier chemical analyses of cell models has provided evidence suggesting a premalignant condition for which distinct chemical profiles can be recorded (1). This information can now be recorded in vivo as part of an MRI scan using a 3T scanner. The aim was to evaluate an early longitudinal study of women carrying the BRCA gene mutations using the 2D L-COSY method to monitor chemical changes in breast tissue that could indicate a progression towards breast cancer that may be identified by escalating lipid deregulation. Six women with BRCA1 gene mutations and 10 women with BRCA2 gene mutations were enrolled in the ongoing study by the Breast and Endocrine Centre in Gateshead, Newcastle, Australia. Patients were assessed by a breast surgeon according to protocol which included mammography, and ultrasound as necessary, to ensure no overt malignancy was present. In vivo 2D L-COSY was recorded at 3T on a Siemens Skyra or Prisma using a 16 channel breast coil. Participants first underwent standard diagnostic contrast enhanced breast MRI, which was reviewed by two independent radiologists using BIRADS scoring. The 15x15x15mm3 spectroscopic voxel was then placed in the lower outer quadrant midway between fibroglandular and fat tissues in the breast. The L-COSY sequence was applied with TE initial 30ms, TR 1.5s, 8 averages per increment, bandwidth 2000 Hz, t1 increment 0.8ms, vector size 1024 points, RF offset frequency 3.2ppm, and 64 increments. The “WET” method of water suppression was applied. Processing was undertaken using previously reported parameters (2). Cross and diagonal peak volumes were measured using Felix software, with the (CH2)n diagonal peak at 1.30 ppm used as the internal chemical shift reference. Due to the absence of a reliable internal concentration standard, peak ratios were calculated with respect to the following reference peaks (F2, F1): (2.75,2.75)ppm; (1.30,1.30)ppm; and (4.25,4.25)ppm. L-COSY was undertaken on patients every 6 months and a full MRI exam every 12 months to examine longitudinal trends. The peak volume ratios of the L-COSY spectrum, identified previously as biomarkers of women carrying the BRCA gene mutations (2), were used to examine longitudinal trends, with the patient’s first scan used as a baseline. To ensure magnet stability a phantom was examined regularly.Examination of longitudinal trends over 30 months in some cases in the biomarker ratios showed that most women exhibited relatively consistent lipid and metabolite ratios over time. Two cases of interest were identified which showed altering biomarker ratios when compared to their baseline scan (Figure 1). The case of interest in the BRCA1 group showed a 35% increase in the lipid crosspeak E signal at (2.02, 1.30) ppm, a 75% decrease in the composite choline resonance at (3.23, 3.23) ppm, and a 74% decreased in the composite choline, glycine and myo-inositol resonance (3.70, 3.70) ppm. The case of interest in the BRCA2 group, where a cancer had been removed from the other breast, showed a 44% increase in the lipid crosspeak E signal, a 62% decrease in the lipid methyl group signal at (0.90,0.90)ppm, and a 70% decrease in the cholesterol methyl group resonance at (0.70,0.70)ppm. Radiological reporting: All cases were BIRADS 1 or BIRADS 2 and showed no MRI changes during the course of the study, including the two cases in which biochemical changes were recorded by 2D L-COSY.This is a follow up study to that where we demonstrated that women carrying the BRCA1 and BRCA2 gene mutations exhibited lipid and metabolite profiles (2) consistent with very early deregulation in cancer cell models (1). Moreover the deregulation was different for BRCA1 and BRCA2. Here we are undertaking a longitudinal study where these same women are monitored every six months. For most women in the study these biomarkers remained relatively stable over time. Of the 6 BRCA1 and 10 BRCA2 patients examined, only one BRCA1 patient and one BRCA2 patient showed further deregulation.