Probing lipids relaxation times in breast cancer using magnetic resonance spectroscopic fingerprinting.

OBJECTIVES: To investigate the clinical relevance of the relaxation times of lipids within breast cancer and normal fibroglandular tissue in vivo, using magnetic resonance spectroscopic fingerprinting (MRSF). METHODS: Twelve patients with biopsy-confirmed breast cancer and 14 healthy controls were prospectively scanned at 3 T using a protocol consisting of diffusion tensor imaging (DTI), MRSF, and dynamic contrast-enhanced (DCE) MRI. Single-voxel MRSF data was recorded from the tumor (patients) - identified using DTI - or normal fibroglandular tissue (controls), in under 20 s. MRSF data was analyzed using in-house software. Linear mixed model analysis was used to compare the relaxation times of lipids in breast cancer VOIs vs. normal fibroglandular tissue. RESULTS: Seven distinguished lipid metabolite peaks were identified and their relaxation times were recorded. Of them, several exhibited statistically significant changes between controls and patients, with strong significance (p < 10-3) recorded for several of the lipid resonances at 1.3 ppm (T1 = 355 ± 17 ms vs. 389 ± 27 ms), 4.1 ppm (T1 = 255 ± 86 ms vs. 127 ± 33 ms), 5.22 ppm (T1 = 724 ± 81 ms vs. 516 ± 62 ms), and 5.31 ppm (T2 = 56 ± 5 ms vs. 44 ± 3.5 ms, respectively). CONCLUSIONS: The application of MRSF to breast cancer imaging is feasible and achievable in clinically relevant scan time. Further studies are required to verify and comprehend the underling biological mechanism behind the differences in lipid relaxation times in cancer and normal fibroglandular tissue. KEY POINTS: •The relaxation times of lipids in breast tissue are potential markers for quantitative characterization of the normal fibroglandular tissue and cancer. •Lipid relaxation times can be acquired rapidly in a clinically relevant manner using a single-voxel technique, termed MRSF. •Relaxation times of T1 at 1.3 ppm, 4.1 ppm, and 5.22 ppm, as well as of T2 at 5.31 ppm, were significantly different between measurements within breast cancer and the normal fibroglandular tissue.

Variations in Practice and Geographic Disparities Between Dedicated Multidisciplinary Clinics for BRCA1/BRCA2 Mutation Carriers in Israel.

BACKGROUND: Population screening for the BRCA mutations in Ashkenazi Jewish women was recently implemented in Israel and is expected to lead to a 10-fold increase in the diagnosis of asymptomatic carriers. Performing the screening follow-up within multidisciplinary dedicated clinics for carriers is recommended for early detection and risk reduction. OBJECTIVES: : To determine the availability, capacity, and practices of dedicated screening clinic for BRCA carriers in Israel. METHODS: A telephone-based survey of all public hospitals in Israel was conducted October 2020 to August 2021 to determine whether they had a dedicated clinic. Dedicated clinics were defined as multidisciplinary screening clinics offering at least breast and gynecological screening and risk reducing services on site. The clinic director or nurse navigator answered a questionnaire about screening practices followed by a semi-structured interview. RESULTS: Of the ten dedicated BRCA clinics found in Israel, nine participated. Approximately 4500 BRCA carriers are currently being followed. No specialized clinics are available in the southern district or in the northernmost half of the northern district of Israel, leading to a disparity between periphery and center. Screening recommendations, although asserted as adhering to international guidelines, vary among clinics including age at initiating of clinical exam, use of adjunct imaging modalities, and follow-up during lactation and after risk reducing surgery. CONCLUSIONS: There is a suboptimal distribution of dedicated clinics for BRCA carriers in Israel. Nationally centralized attempt to create guidelines that will unify screening practices is warranted, especially considering the expected increase in demand.

Health-Related Quality of Life After Nipple-Sparing Mastectomy: Results From the INSPIRE Registry.

INTRODUCTION: Nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) is increasingly used for both breast cancer (TNSM) and risk reduction (RRNSM). The aim of the study is to report the results of the INSPIRE registry assessing health-related quality of life (HRQoL) comparing baseline and 1-year follow-up, regarding surgical indications and chemotherapy (CT) received. METHODS: INSPIRE is a prospective database including women undergoing NSM and IBR from 18 countries. HRQoL was measured using EORTC QLQC30 and QLQ-BR23 before surgery and after 1 year. RESULTS: A total of 677 women were included, of whom 537 (79.3%) underwent TNSM and 140 (21.6%) RRNSM: in total, 806 NSM (556 TNSM and 250 RRNSM). Nipple involvement was present in 7.73% of TNSM and incidental carcinoma in 1.2% of the RRNSM group. Out of the overall 537 patients with systemic treatment, 177 (32.96%) received neoadjuvant chemotherapy (NCT) and 118 (21.92%) adjuvant chemotherapy (CT). A total of 227 patients (28.16%) developed at least one complication postoperatively, 164 (29.5%) in the TNSM group and 63 (25.2%) in the RRNSM group. The TNSM group improved in global health status and emotional functioning after 1 year. No differences were found when comparing HRQoL at 1 year between patients who received NCT and those who received adjuvant CT. The RRNSM group showed improvement in HRQoL, with better emotional functioning and fatigue after 1 year. CONCLUSIONS: This registry reports HRQoL findings after NSM. The impact of CT on worse HRQoL is independent from its timing. Patients with RRNSM showed an improved HRQoL at 1-year follow-up. Discussion of HRQoL outcomes with patients will facilitate the informed decision-making when considering NSM.

Magnetic resonance imaging system for intraoperative margin assessment for DCIS and invasive breast cancer using the ClearSight™ system in breast-conserving surgery-Results from a postmarketing study.

BACKGROUND AND OBJECTIVES: Breast-conserving surgery (BCS) is followed by reoperations in approximately 25%. Reoperations lead to an increased risk of infection and wound healing problems as well as a worse cosmetic outcome. Several technical approaches for an intraoperative margin assessment to decrease the reoperation rate are under evaluation, some of them are still experimental. METHODS: A prospective single-arm post-marketing study with 60 patients undergoing BCS for ductal carcinoma in situ (DCIS) and invasive breast cancer was conducted. The specimen was intraoperatively examined by the ClearSight™ system, a mobile magnetic resonance imaging system that is based on a diffusion-weighted imaging protocol. However, the results were blinded to the surgeon. RESULTS: The ClearSight™ system was performed for both ductal and lobular breast cancer and DCIS, with a sensitivity of 0.80 (95% confidence interval [CI]: 0.44-0.96) and a specificity of 0.84 (95% CI 0.72-0.92), with an overall diagnostic accuracy of 80%. CONCLUSION: Had the ClearSight™ been known to the surgeon intraoperatively, the reoperation rate would have been reduced by 83% for invasive carcinoma, from 10% to 2%, and 50% for DCIS, from 30% to 15% reoperations. A trial designed to examine the impact on reoperation rates is currently ongoing.

Personalized Screening for Breast Cancer: Rationale, Present Practices, and Future Directions.

Ever since screening for early breast cancer (BC) diagnosis was shown to decrease mortality from the disease, screening programs have been widely implemented throughout the world. Targeted age groups and schedules vary between countries but the majority use a population-based approach, regardless of personal BC risk. The purpose of this review was to describe current population-based screening practices, point out some of the shortcomings of these practices, describe BC risk factors and risk assessment models, and present ongoing clinical trials of personalized risk-adapted BC screening. Three ongoing, large-scale, randomized controlled clinical trials (WISDOM in the US, MyPEBS in Europe, and TBST in Italy) were identified through a search of the MEDLINE and US National Library of Medicine (ClinicalTrials.gov) databases. In these trials, women either undergo standard or personalized screening. The trials vary in methods of risk stratification and screening modalities, but all aim to examine whether personalized risk-adapted screening can safely replace the current population-based approach and lead to rates of advanced-stage BC at diagnosis comparable with those of current screening regimens. The results of these trials may change current population-based screening practices.

Diffusivity in breast malignancies analyzed for b > 1000 s/mm2 at 1 mm in-plane resolutions: Insight from Gaussian and non-Gaussian behaviors.

Diffusion-weighted imaging (DWI) can improve breast cancer characterizations, but often suffers from low image quality -particularly at informative b > 1000 s/mm2 values. The aim of this study was to evaluate multishot approaches characterizing Gaussian and non-Gaussian diffusivities in breast cancer. This was a prospective study, in which 15 subjects, including 13 patients with biopsy-confirmed breast cancers, were enrolled. DWI was acquired at 3 T using echo planar imaging (EPI) with and without zoomed excitations, readout-segmented EPI (RESOLVE), and spatiotemporal encoding (SPEN); dynamic contrast-enhanced (DCE) data were collected using three-dimensional gradient-echo T1 weighting; anatomies were evaluated with T2 -weighted two-dimensional turbo spin-echo. Congruence between malignancies delineated by DCE was assessed against high-resolution DWI scans with b-values in the 0-1800 s/mm2 range, as well as against apparent diffusion coefficient (ADC) and kurtosis maps. Data were evaluated by independent magnetic resonance scientists with 3-20 years of experience, and radiologists with 6 and 20 years of experience in breast MRI. Malignancies were assessed from ADC and kurtosis maps, using paired t tests after confirming that these values had a Gaussian distribution. Agreements between DWI and DCE datasets were also evaluated using Sorensen-Dice similarity coefficients. Cancerous and normal tissues were clearly separable by ADCs: by SPEN their average values were (1.03 ± 0.17) × 10-3 and (1.69 ± 0.19) × 10-3  mm2 /s (p < 0.0001); by RESOLVE these values were (1.16 ± 0.16) × 10-3 and (1.52 ± 0.14) × 10-3 (p = 0.00026). Kurtosis also distinguished lesions (K = 0.64 ± 0.15) from normal tissues (K = 0.45 ± 0.05), but only when measured by SPEN (p = 0.0008). The best statistical agreement with DCE-highlighted regions arose for SPEN-based DWIs recorded with b = 1800 s/mm2 (Sorensen-Dice coefficient = 0.67); DWI data recorded with b = 850 and 1200 s/mm2 , led to lower coefficients. Both ADC and kurtosis maps highlighted the breast malignancies, with ADCs providing a more significant separation. The most promising alternative for contrast-free delineations of the cancerous lesions arose from b = 1800 s/mm2 DWI. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 3.

Diagnostic yield of multigene panel testing in an Israeli cohort: enrichment of low-penetrance variants.

BACKGROUND: Carriers of pathogenic variants (PVs) in moderate-high-penetrance cancer susceptibility genes are offered tailored surveillance schemes for early cancer diagnosis. The clinical implications of low-penetrance variant carriers are less clear. METHODS: Clinical and demographic data were retrieved for a cohort of Israeli individuals who underwent oncogenetic testing by the 30-gene cancer panel at Color Genomics laboratory, between 04/2013 and 12/2018. RESULTS: Of 758 genotyped individuals, 504 had been diagnosed with cancer prior to testing: 283 (56%) had breast cancer and 106 (21%) colorectal cancer. Pathogenic or likely pathogenic (P/LP) variants were detected in 123 (16%) individuals. Overall, 44 different P/LP variants were detected in 18/30 cancer susceptibility genes; 20 of them were founder/recurrent mutations. Of the carriers, 39 (32%), 10 (8%), and 74 (60%) carried high-, moderate-, or low-penetrance variants, respectively. After excluding low-penetrance variants, 7% (33/504) of all cancer patients, 6% of breast or ovarian cancer patients were found to be carriers, as well as 7% (14/203) of individuals with colonic polyps, and 4% (11/254) of cancer-free individuals. CONCLUSIONS: The diagnostic yield of moderate- and high-penetrance PVs using multigene panel testing was 6%, with 3.7% carriers of non-recurrent PVs. This yield should be discussed during pre-test counseling, and emphasizes the need for harmonized recommendations regarding clinical implications of low-penetrance variants.

Breast MRI during lactation: effects on tumor conspicuity using dynamic contrast-enhanced (DCE) in comparison with diffusion tensor imaging (DTI) parametric maps.

PURPOSE: To investigate the effect of lactation on breast cancer conspicuity on dynamic contrast-enhanced (DCE) MRI in comparison with diffusion tensor imaging (DTI) parametric maps. MATERIALS AND METHODS: Eleven lactating patients with 16 biopsy-confirmed pregnancy-associated breast cancer (PABC) lesions were prospectively evaluated by DCE and DTI on a 1.5-T MRI for pre-treatment evaluation. Additionally, DCE datasets of 16 non-lactating age-matched breast cancer patients were retrospectively reviewed, as control. Contrast-to-noise ratio (CNR) comprising two regions of interests of the normal parenchyma was used to assess the differences in the tumor conspicuity on DCE subtraction images between lactating and non-lactating patients, as well as in comparison against DTI parametric maps of λ1, λ2, λ3, mean diffusivity (MD), fractional anisotropy (FA), and maximal anisotropy index, λ1-λ3. RESULTS: CNR values of breast cancer on DCE MRI among lactating patients were reduced by 62% and 58% (p < 0.001) in comparison with those in non-lactating patients, when taking into account the normal contralateral parenchyma and an area of marked background parenchymal enhancement (BPE), respectively. Among the lactating patients, DTI parameters of λ1, λ2, λ3, MD, and λ1-λ3 were significantly decreased, and FA was significantly increased in PABC, relative to the normal lactating parenchyma ROIs. When compared against DCE in the lactating cohort, the CNR on λ1, λ2, λ3, and MD was significantly superior, providing up to 138% more tumor conspicuity, on average. CONCLUSION: Breast cancer conspicuity on DCE MRI is markedly reduced during lactation owing to the marked BPE. However, the additional application of DTI can improve the visualization and quantitative characterization of PABC, therefore possibly suggesting an additive value in the diagnostic workup of PABC. KEY POINTS: • Breast cancer conspicuity on DCE MRI has decreased by approximately 60% among lactating patients compared with non-lactating controls. • DTI-derived diffusion coefficients and the anisotropy indices of PABC lesions were significantly different than those of the normal lactating fibroglandular tissue. • Among lactating patients, breast cancer conspicuity on DTI-derived parametric maps provided up to 138% increase in contrast-to-noise ratio compared with DCE imaging.

[DOES NEOADJUVANT CHEMOTHERAPY AFFECT THE IMMEDIATE POSTOPERATIVE COMPLICATION RATE AFTER BREAST RECONSTRUCTION?]

BACKGROUND: Neoadjuvant chemotherapy (NAC) before breast cancer surgery is safe and effective. By reducing the tumor burden, women can achieve complete resections with less extensive operations. Both surgeons and patients share concerns that NAC increases the risk for infection after immediate breast reconstruction, due to its effect on the immune system and the relatively short duration between chemotherapy and surgery. While breast reconstruction plays an increasingly significant role in the treatment of breast cancer, little has been written about the effect of NAC and its impact on post-operative complications. METHODS: We identified 158 patients (205 breasts) who underwent surgery for breast cancer with immediate reconstruction between the years 2013-2017 at the Kaplan Medical Center. Using univariate and multivariate statistics, we compared our patient characteristics according to our main predictor of interest: receiving NAC. We focused on the immediate post-operative complications: infection, skin necrosis, wound dehiscence, hematoma, seroma and implant explantation. RESULTS: Fifty-two patients received NAC and 106 did not. The neoadjuvant group was found to be younger (45 years old vs. 51, P<0.05). The overall complication rate was 30.3%, with a trend towards a lower complication rate in the NAC group, though not statistically significant (23% vs. 34% P=0.2). The overall infection rate was 8.8%, again with a trend towards a lower infection rate among the NAC group (3.8% vs. 11.3% P=0.12). Mastectomy (P=0.02), implant reconstruction (P=0.05) and diabetes (P<0.05) were associated with a higher complication rate. CONCLUSIONS: Our data indicates that NAC is not associated with an increased rate of immediate post-operative complications in women undergoing breast surgery and reconstruction. Therefore, receiving NAC should not be considered a reason to avoid immediate breast reconstruction.

Noncontrast Breast MRI During Pregnancy Using Diffusion Tensor Imaging: A Feasibility Study.

BACKGROUND: Pregnancy-associated breast cancer (PABC) is often a delayed diagnosis and contrast-enhanced MRI is contraindicated because gadolinium agents are known to cross the placenta. PURPOSE: To investigate the feasibility and clinical utility of noncontrast breast MRI using diffusion tensor imaging (DTI) in the diagnostic workup of PABC. STUDY TYPE: Prospective. POPULATION: Between November 2016 and January 2018, 25 pregnant participants (median gestational age: 17 weeks) were recruited from eight referral breast-care centers nationwide. Imaging indications included: newly-diagnosed PABC (n = 10, with 11 lesions), palpable mass/mastitis (n = 4), high-risk screening (n = 10), and monitoring neoadjuvant-chemotherapy response (n = 1). FIELD STRENGTH/SEQUENCE: 1.5T, T2 -weighted, and DTI sequences, prone position, with a scan duration of ∼12 minutes. ASSESSMENT: DTI parametric maps were generated and analyzed at pixel resolution, with reference to ultrasound (US) and pathology. STATISTICAL TESTS: Two-tailed Student's t-test was applied for evaluating differences between DTI parameters of PABC vs. healthy fibroglandular tissue. Pearson's correlation test was applied to measure the agreements between λ1-based longest tumor diameter, US, and pathology. RESULTS: All scans were technically completed and reached diagnostic quality, except one with notable motion artifacts due to positional discomfort, which was excluded. Nine out of 11 known PABC lesions and one newly-diagnosed lesion were visible on λ1, λ2, λ3, mean diffusivity (MD), and λ1-λ3 maps, with substantial parametric contrast compared with the apparently normal contralateral fibroglandular tissue (P < 0.001 for all). Two lesions of 0.7 cm were not depicted by the diffusivity maps. Tumor diameter measured on a thresholded λ1 map correlated well with US (r = 0.97) and pathology (r = 0.95). Malignancy was excluded by DTI parametric maps in scans of symptomatic and high-risk patients, in agreement with US follow-up, except for one false-positive case. DATA CONCLUSION: Noncontrast breast MRI is feasible and well-tolerated during pregnancy. Further studies with a larger and homogeneous cohort are required to validate DTI's additive diagnostic value, albeit this study suggests a potential adjunct role for this noninvasive approach in breast evaluation during pregnancy. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:508-517.

Trans-Vertical Mastectomy With Immediate Implant-Based Reconstruction: A Retrospective, Observational Study.

BACKGROUND: In women with large and ptotic breasts who require a mastectomy and immediate, implant-based reconstruction, long flaps pose a high risk for flap ischemia and necrosis. A new trans-vertical incision for skin-reducing mastectomy is described, which reduces the skin envelope and lifts the breast. OBJECTIVES: The authors sought to describe the new mastectomy access incision and assess its efficacy and safety when followed by immediate implant-based reconstruction. METHODS: This retrospective analysis included 70 consecutive patients (101 breasts) with large and ptotic breasts who underwent a unilateral (n = 39; 55.7%) or bilateral (n = 31; 44.3%), skin-reducing mastectomy utilizing the trans-vertical approach for either breast cancer or risk reduction. All received immediate one- (n = 86; 85.5%) or two-stage (n = 15; 14.5%), implant-based reconstruction utilizing acellular dermal matrix. RESULTS: Mean age was 50.1 years and mean body mass index was 25.6 kg/m2. After a median follow-up of 4.9 years, the number of breasts with minor and major complications was 21 (20.8%) and 26 (25.7%), respectively. The most common major complications were skin-flap necrosis (n = 12; 11.9%) and infection (n = 8; 7.9%). All occurred within 3 months postsurgically. There were 7 cases of capsular contracture (6.9%) and 5 reconstruction failures (5.0%). Higher body mass index (P < 0.01) and breast weight (P < 0.05) were associated with increased complication rates. According to BREAST-Q, 55/64 patients (85.9%) were somewhat or very satisfied with the aesthetic outcome. CONCLUSIONS: The trans-vertical approach is an effective, reproducible, and safe alternative to conventional skin-reducing mastectomy, with favorable aesthetic outcomes, in patients with large and ptotic breasts.

Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy.

PURPOSE: Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion. METHODS: The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology. RESULTS: Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference. CONCLUSIONS: In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques.

Perioperative inhibition of ß-adrenergic and COX2 signaling in a clinical trial in breast cancer patients improves tumor Ki-67 expression, serum cytokine levels, and PBMCs transcriptome.

Catecholamines and prostaglandins are secreted abundantly during the perioperative period in response to stress and surgery, and were shown by translational studies to promote tumor metastasis. Here, in a phase-II biomarker clinical trial in breast cancer patients (n = 38), we tested the combined perioperative use of the ß-blocker, propranolol, and the COX2-inhibitor, etodolac, scheduled for 11 consecutive perioperative days, starting 5 days before surgery. Blood samples were taken before treatment (T1), on the mornings before and after surgery (T2&T3), and after treatment cessation (T4). Drugs were well tolerated. Results based on a-priori hypotheses indicated that already before surgery (T2), serum levels of pro-inflammatory IL-6, CRP, and IFNγ, and anti-inflammatory, cortisol and IL-10, increased. At T2 and/or T3, drug treatment reduced serum levels of the above pro-inflammatory cytokines and of TRAIL, as well as activity of multiple inflammation-related transcription factors (including NFκB, STAT3, ISRE), but not serum levels of cortisol, IL-10, IL-18, IL-8, VEGF and TNFα. In the excised tumor, treatment reduced the expression of the proliferation marker Ki-67, and positively affected its transcription factors SP1 and AhR. Exploratory analyses of transcriptome modulation in PBMCs revealed treatment-induced improvement at T2/T3 in several transcription factors that in primary tumors indicate poor prognosis (CUX1, THRa, EVI1, RORa, PBX1, and T3R), angiogenesis (YY1), EMT (GATA1 and deltaEF1/ZEB1), proliferation (GATA2), and glucocorticoids response (GRE), while increasing the activity of the oncogenes c-MYB and N-MYC. Overall, the drug treatment may benefit breast cancer patients through reducing systemic inflammation and pro-metastatic/pro-growth biomarkers in the excised tumor and PBMCs.

An intraoperative MRI system for margin assessment in breast conserving surgery: Initial results from a novel technique.

BACKGROUND AND OBJECTIVES: One of the major unmet needs in Breast Conserving Surgery (BCS) is a rapid and accurate margin assessment of the lumpectomy specimen. This study evaluates the ability of a novel MRI system (prototype of the ClearSight™ system; Clear-Cut Medical Ltd., Rehovot, Israel) to distinguish malignant and non-malignant tissues in freshly excised breast specimen by comparing MR measurements to histopathology results. METHODS: Seventy-seven samples were obtained from 22 patients undergoing BCS enrolled in the study. A T2* (T2 Star) value in milliseconds (ms) was calculated for each sample and correlated with histopathology results. RESULTS: Of the 77 samples, 35 samples were classified by histopathology as malignant and 42 as non-malignant. T2* values were significantly higher in malignant samples compared to non-malignant samples (15.3 ± 2.72 ms and 10.6 ± 1.47 ms, respectively [P < 0.00001]). Analysis for a determined cutoff of 11.7 ms revealed 91% sensitivity, 93% specificity, and 92% accuracy. ROC curve analysis yielded AUC of 0.97. CONCLUSIONS: This study demonstrates that the system is sensitive and specific in differentiating malignant and non-malignant tissues in freshly excised breast specimen. The system has the potential to be used for breast specimen margin assessment during BCS, with the goal of decreasing the need for re-operation. J. Surg. Oncol. 2016;114:22-26. © 2016 Wiley Periodicals, Inc.

Mapping breast tissue types by miniature radio-frequency near-field spectroscopy sensor in ex-vivo freshly excised specimens.

BACKGROUND: Receiving real-time information on tissue properties while performing biopsy procedures has the potential of improving biopsy accuracy. The study goal was to test the ability of a miniature flexible Radio-Frequency (RF) sensor (Dune Medical Devices), designed to be mounted on the surface of surgical tools, in measuring and mapping the various breast tissue types and abnormalities in terms of electrical properties. METHODS: Between January and October 2012, 102 patients undergoing lumpectomy, open-biopsy or mastectomy, in 3 medical centers, were enrolled in this study. The device was applied to freshly excised specimens, with registration between device measurements and histology analysis. Based on histology, the dielectric properties of the various tissue types were derived. Additionally, the ability of the device to differentiate between malignant and non-malignant tissue was assessed. RESULTS: A total of 4322 measurements from 106 specimens from 102 patients were analyzed. The dielectric properties of 10 tissue types in the low RF-frequency range were measured, showing distinct differences between the various types. Based on the dielectric properties, a score variable was derived, which showed a correlation of 90 % between the RF measurements and the tissue types. Differentiation ability between tissue types was characterized using ROC curve analysis, with AUC of 0.96, and sensitivity and specificity of 90 and 91 % respectively, for tissue feature sizes at or above 0.8 mm. CONCLUSIONS: Using a radio-frequency near-field spectroscopy miniature flexible sensor the dielectric properties of multiple breast tissue types, both normal and abnormal, were evaluated. The results show promise in differentiating between various breast tissue types, and specifically for differentiation between cancer and normal tissues.

Granulomatous Lobular Mastitis.

BACKGROUND: Granulomatous lobular mastitis (GLM) is a rare disorder that can clinically mimic breast carcinoma. The recommendation for diagnosis and treatment of GLM has not yet been established. OBJECTIVES: To assess a series of GLM patients, including their clinical presentation, diagnosis, treatment and outcome. METHODS: We retrospectively analyzed the clinical data and treatment of 17 female patients with biopsy-proven GLM. Breast tissue was obtained by a core needle biopsy (15 patients) or open biopsy (2 patients). Images were reviewed by an experienced radiologist. RESULTS: The mean age of the patients at diagnosis was 44.6 ± 12.6 years. Five patients (29%) presented with bilateral disease, and seven (41%) presented with a mass, suggesting the initial diagnosis of breast carcinoma. Treatment comprised observation alone (23%), antibiotics (58.8%) and/or corticosteroids (with or without methotrexate) (35%). At the end of the study 70.6% of the patients demonstrated complete remission. None of the patients developed any systemic (granulomatous) disease or breast carcinoma during the follow-up period (4.7 ± 3.8 years). CONCLUSIONS: Core needle biopsy is mandatory for the diagnosis of GLM and the exclusion of breast carcinoma. The recommended treatment modalities are observation alone or corticosteroids; surgery should be avoided. GLM is a benign disease with a high rate of resolution and complete remission.

A randomized prospective study of lumpectomy margin assessment with use of MarginProbe in patients with nonpalpable breast malignancies.

BACKGROUND: The presence of tumor cells at the margins of breast lumpectomy specimens is associated with an increased risk of ipsilateral tumor recurrence. Twenty to 30 % of patients undergoing breast-conserving surgery require second procedures to achieve negative margins. This study evaluated the adjunctive use of the MarginProbe device (Dune Medical Devices Ltd, Caesarea, Israel) in providing real-time intraoperative assessment of lumpectomy margins. METHODS: This multicenter randomized trial enrolled patients with nonpalpable breast malignancies. The study evaluated MarginProbe use in addition to standard intraoperative methods for margin assessment. After specimen removal and inspection, patients were randomized to device or control arms. In the device arm, MarginProbe was used to examine the main lumpectomy specimens and direct additional excision of positive margins. Intraoperative imaging was used in both arms; no intraoperative pathology assessment was permitted. RESULTS: In total, 596 patients were enrolled. False-negative rates were 24.8 and 66.1 % and false-positive rates were 53.6 and 16.6 % in the device and control arms, respectively. All positive margins on positive main specimens were resected in 62 % (101 of 163) of cases in the device arm, versus 22 % (33 of 147) in the control arm (p < 0.001). A total of 19.8 % (59 of 298) of patients in the device arm underwent a reexcision procedure compared with 25.8 % (77 of 298) in the control arm (6 % absolute, 23 % relative reduction). The difference in tissue volume removed was not significant. CONCLUSIONS: Adjunctive use of the MarginProbe device during breast-conserving surgery improved surgeons' ability to identify and resect positive lumpectomy margins in the absence of intraoperative pathology assessment, reducing the number of patients requiring reexcision. MarginProbe may aid performance of breast-conserving surgery by reducing the burden of reexcision procedures for patients and the health care system.