Radiological features of screening-detected and interval breast cancers and subsequent survival in Eastern Finnish women.

Interval breast cancers are diagnosed between scheduled screenings and differ in many respects from screening-detected cancers. Studies comparing the survival of patients with interval and screening-detected cancers have reported differing results. The aim of this study was to investigate the radiological and histopathological features and growth rates of screening-detected and interval breast cancers and subsequent survival. This retrospective study included 942 female patients aged 50-69 years with breast cancers treated and followed-up at Kuopio University Hospital between January 2010 and December 2016. The screening-detected and interval cancers were classified as true, minimal-signs, missed, or occult. The radiological features were assessed on mammograms by one of two specialist breast radiologists with over 15 years of experience. A χ2 test was used to examine the association between radiological and pathological variables; an unpaired t test was used to compare the growth rates of missed and minimal-signs cancers; and the Kaplan-Meier estimator was used to examine survival after screening-detected and interval cancers. Sixty occult cancers were excluded, so a total of 882 women (mean age 60.4 ± 5.5 years) were included, in whom 581 had screening-detected cancers and 301 interval cancers. Disease-specific survival, overall survival and disease-free survival were all worse after interval cancer than after screening-detected cancer (p < 0.001), with a mean follow-up period of 8.2 years. There were no statistically significant differences in survival between the subgroups of screening-detected or interval cancers. Missed interval cancers had faster growth rates (0.47% ± 0.77%/day) than missed screening-detected cancers (0.21% ± 0.11%/day). Most cancers (77.2%) occurred in low-density breasts (< 25%). The most common lesion types were masses (73.9%) and calcifications (13.4%), whereas distortions (1.8%) and asymmetries (1.7%) were the least common. Survival was worse after interval cancers than after screening-detected cancers, attributed to their more-aggressive histopathological characteristics, more nodal and distant metastases, and faster growth rates.

Specimen tomosynthesis provides no additional value to specimen ultrasound in ultrasound-visible malignant breast lesions.

BACKGROUND: The aim of this study was to evaluate the accuracy and added value of specimen tomosynthesis (ST) to specimen ultrasound (SUS) in margin assessment of excised breast specimens in breast-conserving therapy for non-palpable US-visible breast lesions. MATERIALS: Between January 2018 and August 2019, all consecutive patients diagnosed with non-palpable breast cancer visible by ultrasound (US), treated with breast-conserving surgery (BCS) and requiring radiological intraoperative breast specimen assessment, were included in this study. Excised breast specimens were examined with SUS by radiologists blinded to the ST results, and margins smaller than 10 mm were recorded. STs were evaluated retrospectively by experienced radiologists. RESULTS: A total of 120 specimens were included. SUS showed a statistically significant correlation with pathological margin measurements, while ST did not and provided no additional information. The odds ratios (ORs) for SUS to predict a positive margin was 3.429 (confidence interval (CI) = 0.548-21.432) using a 10-mm cut-off point and 14.182 (CI = 2.134-94.254) using a 5-mm cut-off point, while the OR for ST were 2.528 (CI = 0.400-15.994) and 3.188 (CI = 0.318-31.998), respectively. CONCLUSIONS: SUS was superior in evaluating intraoperative resection margins of US-visible breast resection specimens when compared to ST. Therefore, ST could be considered redundant in applicable situations.

Diagnostic performance of tomosynthesis, digital mammography and a dedicated digital specimen radiography system versus pathological assessment of excised breast lesions.

BACKGROUND: The aim of the study was to compare the performance of full-field digital mammography (FFDM), digital breast tomosynthesis and a dedicated digital specimen radiography system (SRS) in consecutive patients, and to compare the margin status of resected lesions versus pathological assessment. PATIENTS AND METHODS: Resected tissue specimens from consecutive patients who underwent intraoperative breast specimen assessment following wide local excision or oncoplastic breast conservative surgery were examined by FFDM, tomosynthesis and SRS. Two independent observers retrospectively evaluated the visibility of lesions, size, margins, spiculations, calcifications and diagnostic certainty, and chose the best performing method in a blinded manner. RESULTS: We evaluated 216 specimens from 204 patients. All target malignant lesions were removed with no tumouron-ink. One papilloma had positive microscopic margins and one patient underwent reoperation owing to extensive in situ components. There were no significant differences in measured lesion size among the three methods. However, tomosynthesis was the most accurate modality when compared with the final pathological report. Both observers reported that tomosynthesis had significantly better lesion visibility than SRS and FFDM, which translated into a significantly greater diagnostic certainty. Tomosynthesis was superior to the other two methods in identifying spiculations and calcifications. Both observers reported that tomosynthesis was the best performing method in 76.9% of cases. The interobserver reproducibilities of lesion visibility and diagnostic certainty were high for all three methods. CONCLUSIONS: Tomosynthesis was superior to SRS and FFDM for detecting and evaluating the target lesions, spiculations and calcifications, and was therefore more reliable for assessing complete excision of breast lesions.

Area-based breast percentage density estimation in mammograms using weight-adaptive multitask learning.

Breast density, which is a measure of the relative amount of fibroglandular tissue within the breast area, is one of the most important breast cancer risk factors. Accurate segmentation of fibroglandular tissues and breast area is crucial for computing the breast density. Semiautomatic and fully automatic computer-aided design tools have been developed to estimate the percentage of breast density in mammograms. However, the available approaches are usually limited to specific mammogram views and are inadequate for complete delineation of the pectoral muscle. These tools also perform poorly in cases of data variability and often require an experienced radiologist to adjust the segmentation threshold for fibroglandular tissue within the breast area. This study proposes a new deep learning architecture that automatically estimates the area-based breast percentage density from mammograms using a weight-adaptive multitask learning approach. The proposed approach simultaneously segments the breast and dense tissues and further estimates the breast percentage density. We evaluate the performance of the proposed model in both segmentation and density estimation on an independent evaluation set of 7500 craniocaudal and mediolateral oblique-view mammograms from Kuopio University Hospital, Finland. The proposed multitask segmentation approach outperforms and achieves average relative improvements of 2.88% and 9.78% in terms of F-score compared to the multitask U-net and a fully convolutional neural network, respectively. The estimated breast density values using our approach strongly correlate with radiologists' assessments with a Pearson's correlation of [Formula: see text] (95% confidence interval [0.89, 0.91]). We conclude that our approach greatly improves the segmentation accuracy of the breast area and dense tissues; thus, it can play a vital role in accurately computing the breast density. Our density estimation model considerably reduces the time and effort needed to estimate density values from mammograms by radiologists and therefore, decreases inter- and intra-reader variability.

Dual-Layer Rotation: A Versatile Therapeutic Mammoplasty Technique.

BACKGROUND: Multifocal or complex breast lesions are a challenge for breast-conserving surgery, particularly surgery in small breasts or those located in the upper inner quadrant. The dual-layer rotation technique exploits the idea of manipulating the skin and glandular tissue in separate layers to fill the resection cavity via vertical mammoplasty if skin excision is not required, except in the central area. METHODS: The authors performed a retrospective review of consecutive breast cancer patients who underwent DLR mammoplasty between 2017 and 2019 at a single institution. Clinical data, reoperations, surgical complications, delays in adjuvant treatments, and the need for late revisional surgery were evaluated. Aesthetic outcomes were evaluated objectively and subjectively from photographs. RESULTS: The study included 46 breasts of 40 patients. Tumors were located in the UIQ (30%, 14/46) or in multiple quadrants (22%, 10/46). One third (33%, 13/40) of the patients had a small breast cup size (A-B). Negative margins were primarily achieved in 45 of the 46 breasts. Major complications occurred in three patients, who needed reoperation, and adjuvant therapy was delayed for one of these patients. Late refinement surgery was needed for two patients. The objective and subjective aesthetic outcomes were good or excellent regardless of the tumor position. CONCLUSION: As a novel oncoplastic approach, DLR mammoplasty offers a one-step procedure to treat selected breast cancer patients with challenging resection defects due to different breast sizes or lesion locations. The technique preserves the breast's natural appearance.

Association between breast cancer's prognostic factors and 3D textural features of non-contrast-enhanced T1 weighted breast MRI.

OBJECTIVES: The aim of this exploratory study was to evaluate whether three-dimensional texture analysis (3D-TA) features of non-contrast-enhanced T1 weighted MRI associate with traditional prognostic factors and disease-free survival (DFS) of breast cancer. METHODS: 3D-T1 weighted images from 78 patients with 81 malignant histopathologically verified breast lesions were retrospectively analysed using standard-size volumes of interest. Grey-level co-occurrence matrix (GLCM)-based features were selected for statistical analysis. In statistics the Mann-Whitney U and the Kruskal-Wallis tests, the Cox proportional hazards model and the Kaplan-Meier method were used. RESULTS: Tumours with higher histological grade were significantly associated with higher contrast (1 voxel: p = 0.033, 2 voxels: p = 0.036). All the entropy parameters showed significant correlation with tumour grade (p = 0.015-0.050) but there were no statistically significant associations between other TA parameters and tumour grade. The Nottingham Prognostic Index (NPI) was correlated with contrast and sum entropy parameters. A higher sum variance TA parameter was a significant predictor of shorter DFS. CONCLUSION: Texture parameters, assessed by 3D-TA from non-enhanced T1 weighted images, indicate tumour heterogeneity but have limited independent prognostic value. However, they are associated with tumour grade, NPI, and DFS. These parameters could be used as an adjunct to contrast-enhanced TA parameters. ADVANCES IN KNOWLEDGE: 3D-TA of non-contrast enhanced T1 weighted breast MRI associates with tumour grade, NPI, and DFS. The use of non-contrast 3D-TA parameters in adjunct with contrast-enhanced 3D-TA parameters warrants further research.

Can supine breast magnetic resonance imaging help hit the target in extreme oncoplastic surgery?

OBJECTIVES: To evaluate the clinical value of supine magnetic resonance imaging (MRI) for tumor localization in breast cancer patients with large or multifocal tumors detected by prone MRI, scheduled for oncoplastic breast conserving surgery (OBCS). Outcomes were compared with those of patients who underwent wide local excision (WLE) or OBCS without MRI guidance. METHODS: Over a 2-year period, consecutive patients with large or multifocal disease scheduled for OBCS with MRI-only findings were invited to participate (Group-1). Supplementary supine MRI was performed, and tumor margins were marked in the surgical position. Consecutive patients with early, non-palpable breast cancer who underwent WLE (Group-2) or OBCS (Group-3) were included for comparisons. The primary outcome was reoperation due to an insufficient margin. Secondary outcomes included surgical complications and delayed adjuvant treatment. RESULTS: Altogether, 102 breasts (98 patients) were analyzed. All preoperative demographic data were comparable among the three groups. Multifocality, tumor-to-breast volume ratio, and the volume of excised breast tissue were significantly greater in Group-1 than in Groups-2 and 3. Operation time was longer and the need for axillary clearance or surgery for both breasts was more common in Groups-1 and 3 than in Group-2. Adequate margins were achieved in all patients in Groups-1 and 2, and one patient underwent re-excision in Group-3. CONCLUSIONS: Supine MRI in the surgical position is a new, promising method to localize multifocal, large tumors visible on MRI. Its short-term outcomes were comparable with those of conventional WLE and OBCS.

Multi-level dilated residual network for biomedical image segmentation.

We propose a novel multi-level dilated residual neural network, an extension of the classical U-Net architecture, for biomedical image segmentation. U-Net is the most popular deep neural architecture for biomedical image segmentation, however, despite being state-of-the-art, the model has a few limitations. In this study, we suggest replacing convolutional blocks of the classical U-Net with multi-level dilated residual blocks, resulting in enhanced learning capability. We also propose to incorporate a non-linear multi-level residual blocks into skip connections to reduce the semantic gap and to restore the information lost when concatenating features from encoder to decoder units. We evaluate the proposed approach on five publicly available biomedical datasets with different imaging modalities, including electron microscopy, magnetic resonance imaging, histopathology, and dermoscopy, each with its own segmentation challenges. The proposed approach consistently outperforms the classical U-Net by 2%, 3%, 6%, 8%, and 14% relative improvements in dice coefficient, respectively for magnetic resonance imaging, dermoscopy, histopathology, cell nuclei microscopy, and electron microscopy modalities. The visual assessments of the segmentation results further show that the proposed approach is robust against outliers and preserves better continuity in boundaries compared to the classical U-Net and its variant, MultiResUNet.

Diagnostic performance of the Kaiser score for characterizing lesions on breast MRI with comparison to a multiparametric classification system.

PURPOSE: To determine the diagnostic performance of the Kaiser score and to compare it with the BI-RADS-based multiparametric classification system (MCS). METHOD: Two breast radiologists, blinded to the clinical and pathological information, separately evaluated a database of 499 consecutive patients with structural 3.0 T breast MRI and 697 histopathologically verified lesions. The Kaiser scores and corresponding MCS categories were recorded. The sensitivity and specificity of the Kaiser score and the MCS categories to differentiate benign from malignant lesions were calculated. The interobserver reproducibility and receiver operating characteristic (ROC) parameters were analysed. RESULTS: The sensitivity and specificity of the MCS were 100 % and 12 %, respectively, and those of the Kaiser score were 98.5 % and 34.8 % for reader 1 and 98.7 % and 47.5 % for reader 2. The area under the ROC-curve was 85.9 and 87.6 for readers 1 and 2. The interobserver intraclass correlation coefficient was excellent at 0.882. Reader 1 upgraded six lesions from BI-RADS 3 to a Kaiser score of >4, and reader 2 upgraded seven lesions. When applying the Kaiser score to 158 benign lesions readers 1 and 2 would have reduced the biopsy rate by 22.8 % and 35.4 %, respectively. CONCLUSIONS: The Kaiser score showed high diagnostic accuracy with excellent interobserver reproducibility. The MCS had perfect sensitivity but low specificity. Although the Kaiser score had slightly lower sensitivity, its specificity was 3-4 times greater than that of the MCS. Thus, the Kaiser score has the potential to considerably reduce the biopsy rate for true negative lesions.

The mammographic breast density distribution of Finnish women with breast cancer and comparison of breast density reporting using the 4th and 5th editions of the Breast Imaging-Reporting and Data System.

PURPOSE: To examine the breast density distribution in patients diagnosed with breast cancer in an eastern Finnish population and to examine the changes in breast density reporting patterns between the 4th and 5th editions of the Breast Imaging-Reporting and Data System (BI-RADS). METHOD: 821 women (mean age 62.8 ± 12.2 years, range 28-94 years) with breast cancer were included in this retrospective study and their digital mammographic examinations were assessed semi-automatically and then visually by two radiologists in accordance with the 4th and 5th editions of the BI-RADS. Intraclass correlation coefficients (ICCs) were used to evaluate interobserver reproducibility. Chi-square tests were used to examine the associations between the breast density distribution and age or body mass index (BMI). RESULTS: Interobserver reproducibility of the visual assessment was excellent, with an ICCr = 0.93. The majority of breast cancers occurred in fatty breasts (93.8 %) when density was assessed according to the 4th edition of the BI-RADS. The distributions remained constant after correction for age and BMI. Using the 5th edition, there was an overall 50.2 % decrease in almost entirely fatty (p < 0.001), 19.4 % increase in scattered fibroglandular (p < 0.001), 28.7 % increase in heterogeneously dense (p < 0.001), and 2.1 % increase in extremely dense (p < 0.001) categories. CONCLUSIONS: Most breast cancers in eastern Finland occur in fatty breasts with an area density of < 50 %. Assessing breast density using the 5th edition of the BI-RADS greatly increased denser assessments.

Peritumor to tumor apparent diffusion coefficient ratio is associated with biologically more aggressive breast cancer features and correlates with the prognostication tools.

PURPOSE: The apparent diffusion coefficient (ADC) is increasingly used to characterize breast cancer. The peritumor/tumor ADC ratio is suggested to be a reliable and generally applicable index. However, its overall prognostication value remains unclear. We aimed to evaluate the associations between the peritumor/tumor ADC ratio and histopathological biomarkers and published prognostic tools in patients with invasive breast cancer. MATERIALS AND METHODS: This prospective study included 88 lesions (five bilateral) in 83 patients with primary invasive breast cancer who underwent preoperative 3.0-T magnetic resonance imaging. The lowest intratumoral mean ADC value on the slice with the largest tumor cross-sectional area was designated the tumor ADC, and the highest mean ADC value on the peritumoral breast parenchymal tissue adjacent to the tumor border was designated the peritumor ADC. The peritumor/tumor ADC ratio was then calculated. The tumor and peritumor ADC values and peritumor/tumor ADC ratios were compared with histopathological parameters using an unpaired t test, and their correlations with published prognostic tools were evaluated with Pearson's correlation coefficient. RESULTS: The peritumor/tumor ADC ratio was significantly associated with tumor size (p<0.001), histological grade (p = 0.005), Ki-67 index (p = 0.006), axillary-lymph-node metastasis (p = 0.001), and lymphovascular invasion (p = 0.006), but was not associated with estrogen receptor status (p = 0.931), progesterone receptor status (p = 0.160), or human epidermal growth factor receptor 2 status (p = 0.259). The peritumor/tumor ADC ratio showed moderate positive correlations with the Nottingham Prognostic Index (r = 0.498, p<0.001) and mortality predicted using PREDICT (r = 0.436, p<0.001). CONCLUSION: The peritumor/tumor ADC ratio was correlated with histopathological biomarkers in patients with invasive breast cancer, showed significant correlations with published prognostic indexes, and may provide an easily applicable imaging index for the preoperative prognostic evaluation of breast cancer.

The feasibility of ultrasound-guided vacuum-assisted evacuation of large breast hematomas.

Background Breast hematoma is an often underrated and disregarded post-procedural complication in the literature. Current treatment modalities are comprised of either surgical or expectant therapy, while percutaneous procedures play a smaller role in their treatment. We aimed to examine the efficacy of vacuum-assisted evacuation (VAE) in the treatment of clinically significant large breast hematomas as an alternative to surgery. Patients and methods We retrospectively analysed patients that underwent breast interventions (surgical and percutaneous), who later developed clinically significant large hematomas and underwent a trial of VAE of hematoma in our hospital within the period of four years. Patient and procedure characteristics were acquired before and after VAE. Success of intervention was based on ≥ 50% clearance of hematoma volume and patients' subjective resolution of symptoms. All patients were followed clinically and by ultrasound if needed at different intervals depending on the severity of presenting symptoms. Results Eleven patients were included in the study. The mean largest diameter of hematomas was 7.9 cm and mean surface area was 32.4 cm2. The mean duration of the procedure was 40.5 min. In all patients VAE of hematoma was implemented successfully with no complications. Control visits showed no major residual hematoma or seroma formation. Conclusions Our results show that VAE of hematoma can be implemented as a safe alternative to surgery in large, clinically significant hematomas, regardless of aetiology or duration. The procedure carries less risk, stress and cost with the added benefit of outpatient treatment when compared to surgical treatment.

Peritumoral ADC values in breast cancer: region of interest selection, associations with hyaluronan intensity, and prognostic significance.

OBJECTIVES: We aimed to evaluate the differences in peritumoral apparent diffusion coefficient (ADC) values by four different ROI selection methods and to validate the optimal method. Furthermore, we aimed to evaluate if the peritumor-tumor ADC ratios are correlated with axillary lymph node positivity and hyaluronan accumulation. METHODS: Altogether, 22 breast cancer patients underwent 3.0-T breast MRI, histopathological evaluation, and hyaluronan assay. Paired t and Friedman tests were used to compare minimum, mean, and maximum values of tumoral and peritumoral ADC by four methods: (M1) band ROI, (M2) whole tumor surrounding ROI, (M3) clockwise multiple ROI, and (M4) visual assessment of ROI selection. Subsequently, peritumor/tumor ADC ratios were compared with hyaluronan levels and axillary lymph node status by the Mann-Whitney U test. RESULTS: No statistically significant differences were found among the four ROI selection methods regarding minimum, mean, or maximum values of tumoral and peritumoral ADC. Visual assessment ROI measurements represented the less time-consuming evaluation method for the peritumoral area, and with sufficient accuracy. Peritumor/tumor ADC ratios obtained by all methods except the clockwise ROI (M3) showed a positive correlation with hyaluronan content (M1, p = 0.004; M2, p = 0.012; M3, p = 0.20; M4, p = 0.025) and lymph node metastasis (M1, p = 0.001; M2, p = 0.007; M3, p = 0.22; M4, p = 0.015), which are established factors for unfavorable prognosis. CONCLUSIONS: Our results suggest that the peritumor/tumor ADC ratio could be a readily applicable imaging index associated with axillary lymph node metastasis and extensive hyaluronan accumulation. It could be related to the biological aggressiveness of breast cancer and therefore might serve as an additional prognostic factor. KEY POINTS: • Out of four different ROI selection methods for peritumoral ADC evaluation, measurements based on visual assessment provided sufficient accuracy and were the less time-consuming method. • The peritumor/tumor ADC ratio can provide an easily applicable supplementary imaging index for breast cancer assessment. • A higher peritumor/tumor ADC ratio was associated with axillary lymph node metastasis and extensive hyaluronan accumulation and might serve as an additional prognostic factor.

Tumor microenvironment and breast cancer survival: combined effects of breast fat, M2 macrophages and hyaluronan create a dismal prognosis.

PURPOSE: Tumor microenvironment, including inflammatory cells, adipocytes and extracellular matrix constituents such as hyaluronan (HA), impacts on cancer progression. Systemic metabolism also influences tumor growth e.g. obesity and type 2 diabetes (T2D) are risk factors for breast cancer. Here, in 262 breast cancer cases, we explored the combined impacts on survival of M2-like tumor associated macrophages (TAMs), the abundance of breast fat visualized as low density in mammograms, and tumor HA, and their associations with T2D. METHODS: Mammographic densities were assessed visually from the diagnostic images and dichotomized into very low density (VLD, density ≤ 10%, "fatty breast") and mixed density (MID, density > 10%). The amounts of TAMs (CD163+ and CD68+) and tumor HA were determined by immunohistochemistry. The data of T2D was collected from the patient records. Statistical differences between the parameters were calculated with Chi square or Mann-Whitney test and survival analyses with Cox's model. RESULTS: A combination of fatty breasts (VLD), abundance of M2-like TAMs (CD163+) and tumor HA associated with poor survival, as survival was 88-89% in the absence of these factors but only 40-47% when all three factors were present (p < 0.001). Also, an association between T2D and fatty breasts was found (p < 0.01). Furthermore, tumors in fatty breasts contained more frequently high levels of M2-like TAMs than tumors in MID breasts (p = 0.01). CONCLUSIONS: Our results demonstrate a dramatic effect of the tumor microenvironment on breast cancer progression. We hypothesize that T2D as well as obesity increase the fat content of the breasts, subsequently enhancing local pro-tumoral inflammation.

Galactography is not an obsolete investigation in the evaluation of pathological nipple discharge.

PURPOSE: To evaluate the malignancy rate and diagnostic performance of galactography in patients with pathological nipple discharge (PND) after negative clinical breast examination, mammography and ultrasound. MATERIALS AND METHODS: We retrospectively evaluated all galactograms obtained between January 2006 and December 2014 in women with PND. Galactographic findings were classified into 6 groups according to a modified Galactogram Image Classification system (GICS) to comply with the breast imaging reporting and data system classification. Observers were blinded to the final histology and clinical outcome at the time of analysis. MRI was performed as a problem solving ancillary examination. Imaging findings, pathological diagnosis and follow-up data were evaluated. The diagnostic performance of MRI and technically successful galactography in the detection of neoplastic or risk lesions were separately calculated. RESULTS: A total of 146 patients with PND (mean age, 51.5 years; range, 17-93) were examined. Malignant lesions were detected in only 4 patients (2.7%) and risk-lesions in 5 patients (3.4%). Only one low-grade ductal carcinoma in situ was missed by galactography (GICS 1) and MRI. MRI examinations were performed in 21 (14.4%) patients; one of these patients (4.8%) had a malignant finding (GICS 0), two (9.5%) had risk-lesions (GICS 2 and 5). In the detection of neoplastic or risk lesions the sensitivity and specificity of galactography were 77.4% and 75.7% and of MRI 85.7% and 71.4%, consecutively. CONCLUSION: The malignancy rate is negligible if clinical, mammography, ultrasound and galactography examinations are negative. Galactography remains a practical, valuable and cost-effective examination procedure. If galactography is technically unsuccessful, MRI should be considered as an additional ancillary tool to evaluate the possible etiology of symptoms, but the routine use of MRI in all patients cannot be justified.

UDP-sugar accumulation drives hyaluronan synthesis in breast cancer.

Increased uptake of glucose, a general hallmark of malignant tumors, leads to an accumulation of intermediate metabolites of glycolysis. We investigated whether the high supply of these intermediates promotes their flow into UDP-sugars, and consequently into hyaluronan, a tumor-promoting matrix molecule. We quantified UDP-N-Acetylglucosamine (UDP-GlcNAc) and UDP-glucuronic acid (UDP-GlcUA) in human breast cancer biopsies, the levels of enzymes contributing to their synthesis, and their association with the hyaluronan accumulation in the tumor. The content of UDP-GlcUA was 4 times, and that of UDP-GlcNAc 12 times higher in the tumors as compared to normal glandular tissue obtained from breast reductions. The surge of UDP-GlcNAc correlated with an elevated mRNA expression of glutamine-fructose-6-phosphate aminotransferase 2 (GFAT2), one of the key enzymes in the biosynthesis of UDP-GlcNAc, and the expression of GFAT1 was also elevated. The contents of both UDP-sugars strongly correlated with tumor hyaluronan levels. Interestingly, hyaluronan content did not correlate with the mRNA levels of the hyaluronan synthases (HAS1-3), thus emphasizing the role of the UDP-sugar substrates of these enzymes. The UDP-sugars showed a trend to higher levels in ductal vs. lobular cancer subtypes. The results reveal for the first time a dramatic increase of UDP-sugars in breast cancer, and suggest that their high supply drives the accumulation of hyaluronan, a known promoter of breast cancer and other malignancies. In general, the study shows how the disturbed glucose metabolism typical for malignant tumors can influence cancer microenvironment through UDP-sugars and hyaluronan.

Gadoterate meglumine decreases ADC values of breast lesions depending on the b value combination.

To retrospectively evaluated the influence of administration of the gadolinium based intravenous contrast agent (G-CA) on apparent diffusion coefficient (ADC) values in ADC maps generated using multiple b value combinations. A total of 106 women underwent bilateral 3.0 T breast MRI. As an internal validation, diffusion-weighted imaging (b values of 0, 200, 400, 600, 800 s/mm2) was performed before and after the G-CA (gadoterate meglumine (0.2 ml/kg, 3 ml/s)). Whole lesion and fibroglandular tissue (FGT) covering region-of-interests (ROIs) were drawn on the b = 800 s/mm2 images; ROIs were then propagated to multiple retrospectively generated ADC maps. Twenty-seven patients (mean age 55.8 ± 10.8 years) with 32 mass-like enhancing breast lesions including 25 (78.1 %) histopathologically malignant lesions were enrolled. Lesion ADC values were statistically significantly higher in pre-G-CA than post-G-CA ADC maps (ADC0,200,400,600,800: 1.05 ± 0.35 × 10-3 mm2/s vs. 1.02 ± 0.36 × 10-3 mm2/s (P < 0.05); ADC0,200,400: 1.25 ± 0.42 × 10-3 mm2/s vs. 1.20 ± 0.35 × 10-3 mm2/s (P < 0.05)). ADC values between pre- and post-contrast maps were not statistically different when the maps were generated using other b value combinations. Contrast agent administration did not affect the FGT ADC values. G-CA statistically significantly reduced the ADC values of breast lesions on ADC maps generated using the clinically widely utilized b values.

Quantitative Volumetric K-Means Cluster Segmentation of Fibroglandular Tissue and Skin in Breast MRI.

Mammographic breast density (MBD) is the most commonly used method to assess the volume of fibroglandular tissue (FGT). However, MRI could provide a clinically feasible and more accurate alternative. There were three aims in this study: (1) to evaluate a clinically feasible method to quantify FGT with MRI, (2) to assess the inter-rater agreement of MRI-based volumetric measurements and (3) to compare them to measurements acquired using digital mammography and 3D tomosynthesis. This retrospective study examined 72 women (mean age 52.4 ± 12.3 years) with 105 disease-free breasts undergoing diagnostic 3.0-T breast MRI and either digital mammography or tomosynthesis. Two observers analyzed MRI images for breast and FGT volumes and FGT-% from T1-weighted images (0.7-, 2.0-, and 4.0-mm-thick slices) using K-means clustering, data from histogram, and active contour algorithms. Reference values were obtained with Quantra software. Inter-rater agreement for MRI measurements made with 2-mm-thick slices was excellent: for FGT-%, r = 0.994 (95% CI 0.990-0.997); for breast volume, r = 0.985 (95% CI 0.934-0.994); and for FGT volume, r = 0.979 (95% CI 0.958-0.989). MRI-based FGT-% correlated strongly with MBD in mammography (r = 0.819-0.904, P < 0.001) and moderately to high with MBD in tomosynthesis (r = 0.630-0.738, P < 0.001). K-means clustering-based assessments of the proportion of the fibroglandular tissue in the breast at MRI are highly reproducible. In the future, quantitative assessment of FGT-% to complement visual estimation of FGT should be performed on a more regular basis as it provides a component which can be incorporated into the individual's breast cancer risk stratification.

Is there a Role for Contrast-enhanced Ultrasound in the Detection and Biopsy of MRI Only Visible Breast Lesions?

BACKGROUND: This study aimed to evaluate the feasibility of contrast-enhanced ultrasound (CEUS) and CEUS-guided interventions in the diagnostics of MRI visible targeted US occult breast lesions. PATIENTS AND METHODS: This retrospective study examined 10 females with 10 occult, MRI only detected breast lesions between July 2014 and April 2017. Targeted second look US followed by CEUS with 2.4 ml of SonoVue® were performed for all of the lesions. After positive CEUS localization the same dose was repeated for confirmation and CEUS-guided interventions were performed. RESULTS: MRI revealed 8 mass lesions with a mean size of 9 mm (range 5-16 mm) and 2 non-mass enhancing lesions of 10 and 20 mm in largest diameters. Targeted US revealed no morphological correlate for the lesions. Five out of 10 lesions (50%) were visible on CEUS. CEUS-guided core biopsy was performed on 4 lesions and 1 was marked with a clip for later surgical removal. Histopathological analysis confirmed 4 of them to be malignant. Three out of 5 nonvisible lesions on CEUS underwent MRI-guided interventions, 1 lesion was scheduled for follow-up as it was non-amenable for MRI biopsy, and 1 lesion was biopsied under US-guidance. Three of these nonvisible lesions on CEUS were confirmed to be malignant. CONCLUSIONS: Based on our preliminary results, CEUS is a feasible tool for detecting many MRI only visible breast lesions, resulting in a more cost effective and less time-consuming practice. It is a more convenient alternative than MRI guided biopsy and has the potential to be included in the diagnostic algorithm which evaluates MRI only visible breast lesions.