Race May Not Impact Endocrine Therapy-Related Changes in Breast Density.

BACKGROUND: Reduction in breast density may be a biomarker of endocrine therapy (ET) efficacy. Our objective was to assess the impact of race on ET-related changes in volumetric breast density (VBD). METHODS: This retrospective cohort study assessed longitudinal changes in VBD measures in women with estrogen receptor-positive invasive breast cancer treated with ET. VBD, the ratio of fibroglandular volume (FGV) to breast volume (BV), was measured using Volpara software. Changes in measurements were evaluated using a multivariable linear mixed effects model. RESULTS: Compared with white women (n = 191), black women (n = 107) had higher rates of obesity [mean ± SD body mass index (BMI) 34.5 ± 9.1 kg/m2 vs. 30.6 ± 7.0 kg/m2, P < 0.001] and premenopausal status (32.7% vs. 16.7%, P = 0.002). Age- and BMI-adjusted baseline FGV, BV, and VBD were similar between groups. Modeled longitudinal changes were also similar: During a follow-up of 30.7 ± 15.0 months (mean ± SD), FGV decreased over time in premenopausal women (slope = -0.323 cm3; SE = 0.093; P = 0.001), BV increased overall (slope = 2.475 cm3; SE = 0.483; P < 0.0001), and VBD decreased (premenopausal slope = -0.063%, SE = 0.011; postmenopausal slope = -0.016%, SE = 0.004; P < 0.0001). Race was not significantly associated with these longitudinal changes, nor did race modify the effect of time on these changes. Higher BMI was associated with lower baseline VBD (P < 0.0001). Among premenopausal women, VBD declined more steeply for women with lower BMI (time × BMI, P = 0.0098). CONCLUSIONS: Race does not appear to impact ET-related longitudinal changes in VBD. IMPACT: Racial disparities in estrogen receptor-positive breast cancer recurrence and mortality may not be explained by differential declines in breast density due to ET.

Transverse relaxation-based assessment of mammographic density and breast tissue composition by single-sided portable NMR.

PURPOSE: Elevated mammographic density (MD) is an independent risk factor for breast cancer (BC) as well as a source of masking in X-ray mammography. High-frequency longitudinal monitoring of MD could also be beneficial in hormonal BC prevention, where early MD changes herald the treatment's success. We present a novel approach to quantification of MD in breast tissue using single-sided portable NMR. Its development was motivated by the low cost of portable-NMR instrumentation, the suitability for measurements in vivo, and the absence of ionizing radiation. METHODS: Five breast slices were obtained from three patients undergoing prophylactic mastectomy or breast reduction surgery. Carr-Purcell-Meiboom-Gill (CPMG) relaxation curves were measured from (1) regions of high and low MD (HMD and LMD, respectively) in the full breast slices; (2) the same regions excised from the full slices; and (3) excised samples after H2 O-D2 O replacement. T2 distributions were reconstructed from the CPMG decays using inverse Laplace transform. RESULTS: Two major peaks, identified as fat and water, were consistently observed in the T2 distributions of HMD regions. The LMD T2 distributions were dominated by the fat peak. The relative areas of the two peaks exhibited statistically significant (P < .005) differences between HMD and LMD regions, enabling their classification as HMD or LMD. The relative-area distributions exhibited no statistically significant differences between full slices and excised samples. CONCLUSION: T2 -based portable-NMR analysis is a novel approach to MD quantification. The ability to quantify tissue composition, combined with the low cost of instrumentation, make this approach promising for clinical applications.

Intra-operative spectroscopic assessment of surgical margins during breast conserving surgery.

BACKGROUND: In over 20% of breast conserving operations, postoperative pathological assessment of the excised tissue reveals positive margins, requiring additional surgery. Current techniques for intra-operative assessment of tumor margins are insufficient in accuracy or resolution to reliably detect small tumors. There is a distinct need for a fast technique to accurately identify tumors smaller than 1 mm2 in large tissue surfaces within 30 min. METHODS: Multi-modal spectral histopathology (MSH), a multimodal imaging technique combining tissue auto-fluorescence and Raman spectroscopy was used to detect microscopic residual tumor at the surface of the excised breast tissue. New algorithms were developed to optimally utilize auto-fluorescence images to guide Raman measurements and achieve the required detection accuracy over large tissue surfaces (up to 4 × 6.5 cm2). Algorithms were trained on 91 breast tissue samples from 65 patients. RESULTS: Independent tests on 121 samples from 107 patients - including 51 fresh, whole excision specimens - detected breast carcinoma on the tissue surface with 95% sensitivity and 82% specificity. One surface of each uncut excision specimen was measured in 12-24 min. The combination of high spatial-resolution auto-fluorescence with specific diagnosis by Raman spectroscopy allows reliable detection even for invasive carcinoma or ductal carcinoma in situ smaller than 1 mm2. CONCLUSIONS: This study provides evidence that this multimodal approach could provide an objective tool for intra-operative assessment of breast conserving surgery margins, reducing the risk for unnecessary second operations.

Mean glandular dose to patients from stereotactic breast biopsy procedures.

The aim of this work is to study the radiation doses delivered to a group of patients that underwent a stereotactic breast biopsy (SBB) procedure. Mean glandular doses (MGD) were estimated from the air-kerma measured at the breast surface entrance multiplying by specific conversion coefficients (DgN) that were estimated using Monte Carlo simulations. DgN were calculated for the 0° and ±15° projections used in SBB and for the particular beam quality. Data on 61 patients were collected showing that a typical SBB procedure is composed by ten images. MGD was on average (4 ± 2) mGy with (0.38 ± 0.06) mGy per image. The use of specific conversion coefficients instead of typical DgN for mammography/tomosynthesis yields to obtain MGD values for SBB that are around a 65% lower on average.

Mean glandular dose coefficients (D(g)N) for x-ray spectra used in contemporary breast imaging systems.

To develop tables of normalized glandular dose coefficients D(g)N for a range of anode-filter combinations and tube voltages used in contemporary breast imaging systems. Previously published mono-energetic D(g)N values were used with various spectra to mathematically compute D(g)N coefficients. The tungsten anode spectra from TASMICS were used; molybdenum and rhodium anode-spectra were generated using MCNPX Monte Carlo code. The spectra were filtered with various thicknesses of Al, Rh, Mo or Cu. An initial half value layer (HVL) calculation was made using the anode and filter material. A range of the HVL values was produced with the addition of small thicknesses of polymethyl methacrylate (PMMA) as a surrogate for the breast compression paddle, to produce a range of HVL values at each tube voltage. Using a spectral weighting method, D(g)N coefficients for the generated spectra were calculated for breast glandular densities of 0%, 12.5%, 25%, 37.5%, 50% and 100% for a range of compressed breast thicknesses from 3 to 8 cm. Eleven tables of normalized glandular dose (D(g)N) coefficients were produced for the following anode/filter combinations: W + 50 µm Ag, W + 500 µm Al, W + 700 µm Al, W + 200 µm Cu, W + 300 µm Cu, W + 50 µm Rh, Mo + 400 µm Cu, Mo + 30 µm Mo, Mo + 25 µm Rh, Rh + 400 µm Cu and Rh + 25 µm Rh. Where possible, these results were compared to previously published D(g)N values and were found to be on average less than 2% different than previously reported values.Over 200 pages of D(g)N coefficients were computed for modeled x-ray system spectra that are used in a number of new breast imaging applications. The reported values were found to be in excellent agreement when compared to published values.

Monte Carlo simulation for the estimation of the glandular breast dose for a digital breast tomosynthesis system.

Digital breast tomosynthesis (DBT) is a screening and diagnostic modality that acquires images of the breast at multiple angles during a short scan. The Selenia Dimensions (Hologic, Bedford, Mass) DBT system can perform both full-field digital mammography and DBT. The system acquires 15 projections over a 15° angular range (from -7.5° to +7.5°). An important factor in determining the optimal imaging technique for breast tomosynthesis is the radiation dose. In breast imaging, the radiation dose of concern is that deposited in the glandular tissue of the breast because this is the tissue that has a risk of developing cancer. The concept of the normalised mean glandular dose (DgN) has been introduced as the metric for the dose in breast imaging. The DgN is difficult to measure. The Monte Carlo techniques offer an alternative method for a realistic estimation of the radiation dose. The purpose of this work was to use the Monte Carlo code MCNPX technique to generate monoenergetic glandular dose data for estimating the breast tissue dose in tomosynthesis for arbitrary spectra as well as to observe the deposited radiation dose by projection on the glandular portion of the breast in a Selenia Dimensions DBT system. A Monte Carlo simulation of the system was developed to compute the DgN in a craniocaudal view. Monoenergetic X-ray beams from 10 to 49 keV in 1-keV increments were used. The simulation utilised the assumption of a homogeneous breast composition and three compositions (0 % glandular, 50 % glandular and 100 % glandular). The glandular and adipose tissue compositions were specified according ICRU Report 44. A skin layer of 4 mm was assumed to encapsulate the breast on all surfaces. The breast size was varied using the chest wall-to-nipple distance (CND) and compressed breast thickness (t). In this work, the authors assumed a CND of 5 cm and the thicknesses ranged from 2 to 8 cm, in steps of 2 cm. The fractional energy absorption increases (up to 44.35 % between 0 % glandular and 100 % glandular) with the increase in the glandular fraction due to changing the composition and increasing the density. Low-energy photon absorption occurred in the first tissue layer. The DgN decreases with increasing the compressed breast thickness. The graphs show that between 15 and 30 keV provides the greatest contribution to the dose and that the glandular dose is almost constant as a function of the projection angle. The results may be useful for optimising tomosynthesis procedures and evaluating the dose distribution in the projections in a craniocaudal view.

Breast density assessment using a 3T MRI system: comparison among different sequences.

PURPOSE: To compare MRI sequences for breast density measurements on a 3T MRI system using IDEAL (Iterative Decomposition of water and fat with Echo Asymmetry and Least squares estimation) as possible physiology-like reference. MATERIALS AND METHODS: MRI examination was performed in 48 consecutive patients (mean age 41, years; range, 35-67 years) on a 3.0T scanner and 46 were included. All (fertile) women, were examined between days 5 and 15 of their menstrual cycle. MRI protocol included: T1-turbo spin-echo (T1-tSE), T2-turbo spin-echo (T2-tSE), VIBRANT (Volume Imaging for Breast Assessment) before and after injection of contrast media and IDEAL. Breast density was calculated with semi-automated software. Statistical analysis was performed with non-parametric tests. RESULTS: Mean percentage of breast density calculated in each sequence was: T1-tSE = 56%; T2-tSE  = 52%; IDEAL FatOnly  = 55%; IDEAL WaterOnly  = 53%, VIBRANT = 55%. Significant differences were observed between T2-tSE and both T1-tSE (p<0.001), VIBRANT sequences (p = 0.009), T1-tSE and both IDEAL WaterOnly (p = 0.007) and IDEAL FatOnly (p = 0.047). Breast density percentage showed a positive linear correlation among different sequences: r ≥ 0.93. CONCLUSIONS: Differences exist between MRI sequences used to assess breast density percentage. T1-weighted sequences values were similar to IDEAL sequences.

Rheological assessment of a polymeric spherical structure using a three-dimensional shear wave scattering model in dynamic spectroscopy elastography.

With the purpose of assessing localized rheological behavior of pathological tissues using ultrasound dynamic elastography, an analytical shear wave scattering model was used in an inverse problem framework. The proposed method was adopted to estimate the complex shear modulus of viscoelastic spheres from 200 to 450 Hz. The inverse problem was formulated and solved in the frequency domain, allowing assessment of the complex viscoelastic shear modulus at discrete frequencies. A representative rheological model of the spherical obstacle was determined by comparing storage and loss modulus behaviors with Kelvin-Voigt, Maxwell, Zener, and Jeffrey models. The proposed inversion method was validated by using an external vibrating source and acoustic radiation force. The estimation of viscoelastic properties of three-dimensional spheres made softer or harder than surrounding tissues did not require a priori rheological assumptions. The proposed method is intended to be applied in the context of breast cancer imaging.

Investigation of absorbed radiation dose in refraction-enhanced breast tomosynthesis by a Laue case analyser.

An early diagnosis system for breast cancer using refraction-enhanced breast tomosynthesis is under development. Tomograms of breast specimens based on refraction-contrast were demonstrated using the simplest shift-and-add tomosynthesis algorithm. Raw projection image data of breast specimens for tomosynthesis were acquired for a total of 51 views over an angle of 50°, in increments of 1°, by rotating the object. The incident X ray was monochromatic synchrotron radiation with 20 keV. The purpose of this study was to estimate the absorbed dose of a new X-ray imaging method. As breast cancer almost always arises in glandular breast tissue, the average absorbed dose in such glandular tissue should be measured to estimate the radiation risk associated with mammography. The absorbed dose of the mammary gland due to monochromatic X rays was calculated by the Monte Carlo method, and the optimal X ray energy range for refraction-enhanced breast tomosynthesis was investigated through actual measurements. Compared with the conventional method, it was found to be below one-sixth per inspection.

Influence of breast composition and interseed attenuation in dose calculations for post-implant assessment of permanent breast 103Pd seed implant.

The impact of tissue heterogeneity and interseed attenuation is studied in post-implant evaluation of five clinical permanent breast (103)Pd seed implants using the Monte Carlo (MC) dose calculation method. Dose metrics for the target (PTV) as well as an organ at risk (skin) are used to visualize the differences between a TG43-like MC method and more accurate MC methods capable of considering the breast tissue heterogeneity as well as the interseed attenuation. PTV dose is reduced when using a breast tissue model instead of water in MC calculations while the dose to the skin is increased. Furthermore, we investigate the effect of varying the glandular/adipose proportion of the breast tissue on dose distributions. The dose to the PTV (skin) decreases (increases) with the increasing adipose proportion inside the breast. In a complete geometry and compared to a TG43-like situation, the average PTV D(90) reduction varies from 3.9% in a glandular breast to 35.5% when the breast consists entirely of adipose. The skin D(10) increases by 28.2% in an entirely adipose breast. The results of this work show the importance of an accurate and patient-dependent breast tissue model to be used in the dosimetry for this kind of low energy implant.

Noninvasive assessment of breast cancer risk using time-resolved diffuse optical spectroscopy.

Breast density is a recognized strong and independent risk factor for breast cancer. We propose the use of time-resolved transmittance spectroscopy to estimate breast tissue density and potentially provide even more direct information on breast cancer risk. Time-resolved optical mammography at seven wavelengths (635 to 1060 nm) is performed on 49 subjects. Average information on breast tissue of each subject is obtained on oxy- and deoxyhemoglobin, water, lipids, and collagen content, as well as scattering amplitude and power. All parameters, except for blood volume and oxygenation, correlate with mammographic breast density, even if not to the same extent. A synthetic optical index proves to be quite effective in separating different breast density categories. Finally, the estimate of collagen content as a more direct means for the assessment of breast cancer risk is discussed.

Computation of the glandular radiation dose in digital tomosynthesis of the breast.

Tomosynthesis of the breast is currently a topic of intense interest as a logical next step in the evolution of digital mammography. This study reports on the computation of glandular radiation dose in digital tomosynthesis of the breast. Previously, glandular dose estimations in tomosynthesis have been performed using data from studies of radiation dose in conventional planar mammography. This study evaluates, using Monte Carlo methods, the normalized glandular dose (DgN) to the breast during a tomosynthesis study, and characterizes its dependence on breast size, tissue composition, and x-ray spectrum. The conditions during digital tomosynthesis imaging of the breast were simulated using a computer program based on the Geant4 toolkit. With the use of simulated breasts of varying size, thickness and tissue composition, the DgN to the breast tissue was computed for varying x-ray spectra and tomosynthesis projection angle. Tomosynthesis projections centered about both the cranio-caudal (CC) and medio-lateral oblique (MLO) views were simulated. For each projection angle, the ratio of the glandular dose for that projection to the glandular dose for the zero degree projection was computed. This ratio was denoted the relative glandular dose (RGD) coefficient, and its variation under different imaging parameters was analyzed. Within mammographic energies, the RGD was found to have a weak dependence on glandular fraction and x-ray spectrum for both views. A substantial dependence on breast size and thickness was found for the MLO view, and to a lesser extent for the CC view. Although RGD values deviate substantially from unity as a function of projection angle, the RGD averaged over all projections in a complete tomosynthesis study varies from 0.91 to 1.01. The RGD results were fit to mathematical functions and the resulting equations are provided.