Breast Cancer Mortality among Women with a BRCA1 or BRCA2 Mutation in a Magnetic Resonance Imaging Plus Mammography Screening Program.

Annual breast magnetic resonance imaging (MRI) plus mammography is the standard of care for screening women with inherited BRCA1/2 mutations. However, long-term breast cancer-related mortality with screening is unknown. Between 1997 and June 2011, 489 previously unaffected BRCA1/2 mutation carriers aged 25 to 65 years were screened with annual MRI plus mammography on our study. Thereafter, participants were eligible to continue MRI screening through the high-risk Ontario Breast Screening Program. In 2019, our data were linked to the Ontario Cancer Registry of Cancer Care Ontario to identify all incident cancers, vital status and causes of death. Observed breast cancer mortality was compared to expected mortality for age-matched women in the general population. There were 91 women diagnosed with breast cancer (72 invasive and 19 ductal carcinoma in situ (DCIS)) with median follow-up 7.4 (range: 0.1 to 19.2) years. Four deaths from breast cancer were observed, compared to 2.0 deaths expected (standardized mortality ratio (SMR) 2.0, p = 0.14). For the 489 women in the study, the probability of not dying of breast cancer at 20 years from the date of the first MRI was 98.2%. Annual screening with MRI plus mammography is a reasonable option for women who decline or defer risk-reducing mastectomy.

Differences in natural history between breast cancers in BRCA1 and BRCA2 mutation carriers and effects of MRI screening-MRISC, MARIBS, and Canadian studies combined.

BACKGROUND: It is recommended that BRCA1/2 mutation carriers undergo breast cancer screening using MRI because of their very high cancer risk and the high sensitivity of MRI in detecting invasive cancers. Clinical observations suggest important differences in the natural history between breast cancers due to mutations in BRCA1 and BRCA2, potentially requiring different screening guidelines. METHODS: Three studies of mutation carriers using annual MRI and mammography were analyzed. Separate natural history models for BRCA1 and BRCA2 were calibrated to the results of these studies and used to predict the impact of various screening protocols on detection characteristics and mortality. RESULTS: BRCA1/2 mutation carriers (N = 1,275) participated in the studies and 124 cancers (99 invasive) were diagnosed. Cancers detected in BRCA2 mutation carriers were smaller [80% ductal carcinoma in situ (DCIS) or ≤10 mm vs. 49% for BRCA1, P < 0.001]. Below the age of 40, one (invasive) cancer of the 25 screen-detected cancers in BRCA1 mutation carriers was detected by mammography alone, compared with seven (three invasive) of 11 screen-detected cancers in BRCA2 (P < 0.0001). In the model, the preclinical period during which cancer is screen-detectable was 1 to 4 years for BRCA1 and 2 to 7 years for BRCA2. The model predicted breast cancer mortality reductions of 42% to 47% for mammography, 48% to 61% for MRI, and 50% to 62% for combined screening. CONCLUSIONS: Our studies suggest substantial mortality benefits in using MRI to screen BRCA1/2 mutation carriers aged 25 to 60 years but show important clinical differences in natural history. IMPACT: BRCA1 and BRCA2 mutation carriers may benefit from different screening protocols, for example, below the age of 40.

The influence of radial undersampling schemes on compressed sensing reconstruction in breast MRI.

Fast imaging applications in magnetic resonance imaging (MRI) frequently involve undersampling of k-space data to achieve the desired temporal resolution. However, high temporal resolution images generated from undersampled data suffer from aliasing artifacts. In radial k-space sampling, this manifests as undesirable streaks that obscure image detail. Compressed sensing reconstruction has been shown to reduce such streak artifacts, based on the assumption of image sparsity. Here, compressed sensing is implemented with three different radial sampling schemes (golden-angle, bit-reversed, and random sampling), which are compared over a range of spatiotemporal resolutions. The sampling methods are implemented in static scenarios where different undersampling patterns could be compared. Results from point spread function studies, simulations, phantom and in vivo experiments show that the choice of radial sampling pattern influences the quality of the final image reconstructed by the compressed sensing algorithm. While evenly undersampled radial trajectories are best for specific temporal resolutions, golden-angle radial sampling results in the least overall error when various temporal resolutions are considered. Reduced temporal fluctuations from aliasing artifacts in golden-angle sampling translates to improved compressed sensing reconstructions overall.

Temporal stability of adaptive 3D radial MRI using multidimensional golden means.

Breast tumor diagnosis requires both high spatial resolution to obtain information about tumor morphology and high temporal resolution to probe the kinetics of contrast uptake. Adaptive sampling of k-space allows images in dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) to be reconstructed at various spatial or temporal resolutions from the same dataset. However, conventional radial approaches have limited flexibility that restricts image reconstruction to predetermined resolutions. Golden-angle radial k-space sampling achieves flexibility in-plane with samples that are incremented by the golden angle, which fills two-dimensional (2D) k-space with radial spokes that have a relatively uniform angular distribution for any time interval. We extend this method to three-dimensional (3D) radial sampling, or 3D-Projection Reconstruction (3D-PR) using multidimensional golden means, which are derived from modified Fibonacci sequences by an eigenvalue approach. We quantitatively compare this technique to conventional 3D radial methods in terms of the fluctuation in error caused by undersampling artifacts, and show that the golden 3D-PR method can substantially improve the temporal stability of quantitative measurements made from dynamic images when compared to conventional 3D radial approaches of k-space sampling.

Comparison of biphasic and reordered fat suppression for dynamic breast MRI.

PURPOSE: To optimize a reordered k-space acquisition that applies intermittent fat saturation (FS) pulses to allow for a time-efficient reduction of fat signal in breast MR images, and compare it with an elliptic-centric biphasic FS method in terms of the degree of fat suppression and speed. MATERIALS AND METHODS: The behavior of the fat and water signals under the influence of the reordered sequence was characterized. This allowed us to optimize the flip angle and visualize the expected artifacts by deriving the point spread function (PSF) of the fat signal. We compared the two sequences by acquiring images with a varying number of FS pulses, with a corresponding difference in scan time. The quality of the images was assessed by comparison with images obtained with full fat suppression as measured by a root-mean-square (RMS) error metric. RESULTS: The reordered sequence allowed for an approximately twofold reduction in error compared to the biphasic sequence for the same scan time. With the reordered sequence and optimized scan parameters, we were able to reduce the time spent on fat suppression by as much as 99% with no discernible reduction in image quality. CONCLUSION: This method will allow robust fat suppression with virtually no extension in imaging time for dynamic contrast-enhanced (DCE)-MRI.

Dietary organic isothiocyanates are cytotoxic in human breast cancer MCF-7 and mammary epithelial MCF-12A cell lines.

Organic isothiocyanates (ITCs) are dietary components present in cruciferous vegetables. The purpose of this investigation was to examine the cytotoxicity of 1-naphthyl isothiocyanate (NITC), benzyl isothiocyanate (BITC), beta-phenethyl isothiocyanate (PEITC), and sulforaphane in human breast cancer MCF-7 and human mammary epithelium MCF-12A cell lines, as well as in a second human epithelial cell line, human kidney HK-2 cells. The cytotoxicity of NITC, BITC, PEITC, and sulforaphane, as well as the cytotoxicity of the chemotherapeutic agents daunomycin (DNM) and vinblastine (VBL), were examined in MCF-7/sensitive (wt), MCF-7/Adr (which overexpresses P-glycoprotein), MCF-12A, and HK-2 cells. Cell growth was determined by a sulforhodamine B assay. The IC50 values for DNM and VBL in MCF-7/Adr cells were 7.12 +/- 0.42 microM and 0.106 +/- 0.004 microM (mean +/- SE) following a 48-hr exposure; IC50 values for BITC, PEITC, NITC, and sulforaphane were 5.95 +/- 0.10, 7.32 +/- 0.25, 77.9 +/- 8.03, and 13.7 +/- 0.82 microM, respectively, with similar values obtained in MCF-7/wt cells. Corresponding values for BITC, PEITC, NITC, and sulforaphane in MCF-12A cells were 8.07 +/- 0.29, 7.71 +/- 0.07, 33.6 +/- 1.69, and 40.5 +/- 1.25 microM, respectively. BITC and PEITC can inhibit the growth of human breast cancer cells as well as human mammary epithelium cells at concentrations similar to those of the chemotherapeutic drug DNM. Sulforaphane and NITC exhibited higher IC50 values. The effect of these ITCs on cell growth may contribute to the cancer chemopreventive properties of ITCs by suppressing the growth of preclinical tumors, and may indicate a potential use of these compounds as chemotherapeutic agents in cancer treatment.

Comparison of MR imaging breast coils.

In one volunteer, five breast coils were evaluated for signal-to-noise ratio (SNR), uniformity, comfort, subject orientation, access to the breast, and unilateral imaging options. The four-coil arrays provided superior SNR, imaging flexibility, and access. Uniformity and comfort were issues with all coils. Substantial design differences exist between coils; purchasers should ensure that their specific requirements are met.