Current and future diagnostic and treatment strategies for patients with invasive lobular breast cancer.

BACKGROUND: Invasive lobular breast cancer (ILC) is the second most common type of breast cancer after invasive breast cancer of no special type (NST), representing up to 15% of all breast cancers. DESIGN: Latest data on ILC are presented, focusing on diagnosis, molecular make-up according to the European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets (ESCAT) guidelines, treatment in the early and metastatic setting and ILC-focused clinical trials. RESULTS: At the imaging level, magnetic resonance imaging-based and novel positron emission tomography/computed tomography-based techniques can overcome the limitations of currently used imaging techniques for diagnosing ILC. At the pathology level, E-cadherin immunohistochemistry could help improving inter-pathologist agreement. The majority of patients with ILC do not seem to benefit as much from (neo-)adjuvant chemotherapy as patients with NST, although chemotherapy might be required in a subset of high-risk patients. No differences in treatment efficacy are seen for anti-human epidermal growth factor receptor 2 (HER2) therapies in the adjuvant setting and cyclin-dependent kinases 4 and 6 inhibitors in the metastatic setting. The clinical utility of the commercially available prognostic gene expression-based tests is unclear for patients with ILC. Several ESCAT alterations differ in frequency between ILC and NST. Germline BRCA1 and PALB2 alterations are less frequent in patients with ILC, while germline CDH1 (gene coding for E-cadherin) alterations are more frequent in patients with ILC. Somatic HER2 mutations are more frequent in ILC, especially in metastases (15% ILC versus 5% NST). A high tumour mutational burden, relevant for immune checkpoint inhibition, is more frequent in ILC metastases (16%) than in NST metastases (5%). Tumours with somatic inactivating CDH1 mutations may be vulnerable for treatment with ROS1 inhibitors, a concept currently investigated in early and metastatic ILC. CONCLUSION: ILC is a unique malignancy based on its pathological and biological features leading to differences in diagnosis as well as in treatment response, resistance and targets as compared to NST.

Flemish breast cancer screening programme: 15 years of key performance indicators (2002-2016).

BACKGROUND: We examined 15 years of key performance indicators (KPIs) of the population-based mammography screening programme (PMSP) in Flanders, Belgium. METHODS: Individual screening data were linked to the national cancer registry to obtain oncological follow-up. We benchmarked crude KPI results against KPI-targets set by the European guidelines and KPI results of other national screening programmes. Temporal trends were examined by plotting age-standardised KPIs against the year of screening and estimating the Average Annual Percentage Change (AAPC). RESULTS: PMSP coverage increased significantly over the period of 15 years (+ 7.5% AAPC), but the increase fell to + 1.6% after invitation coverage was maximised. In 2016, PMSP coverage was at 50.0% and opportunistic coverage was at 14.1%, resulting in a total coverage by screening of 64.2%. The response to the invitations was 49.8% in 2016, without a trend. Recall rate decreased significantly (AAPC -1.5% & -5.0% in initial and subsequent regular screenings respectively) while cancer detection remained stable (AAPC 0.0%). The result was an increased positive predictive value (AAPC + 3.8%). Overall programme sensitivity was stable and was at 65.1% in 2014. In initial screens of 2015, the proportion of DCIS, tumours stage II+, and node negative invasive cancers was 18.2, 31.2, and 61.6% respectively. In subsequent regular screens of 2015, those proportions were 14.0, 24.8, and 65.4% respectively. Trends were not significant. CONCLUSION: Besides a suboptimal attendance rate, most KPIs in the Flemish PMSP meet EU benchmark targets. Nonetheless, there are several priorities for further investigation such as a critical evaluation of strategies to increase screening participation, organising a biennial radiological review of interval cancers, analysing the effect that preceding opportunistic screening has on the KPI for initial screenings, and efforts to estimate the impact on breast cancer mortality.

Design and application of a structured phantom for detection performance comparison between breast tomosynthesis and digital mammography.

This paper introduces and applies a structured phantom with inserted target objects for the comparison of detection performance of digital breast tomosynthesis (DBT) against 2D full field digital mammography (FFDM). The phantom consists of a 48 mm thick breast-shaped polymethyl methacrylate (PMMA) container filled with water and PMMA spheres of different diameters. Three-dimensionally (3D) printed spiculated masses (diameter range: 3.8-9.7 mm) and non-spiculated masses (1.6-6.2 mm) along with microcalcifications (90-250 µm) were inserted as targets. Reproducibility of the phantom application was studied on a single system using 30 acquisitions. Next, the phantom was evaluated on five different combined FFDM & DBT systems and target detection was compared for FFDM and DBT modes. Ten phantom images in both FFDM and DBT modes were acquired on these 5 systems using automatic exposure control. Five readers evaluated target detectability. Images were read with the four-alternative forced-choice (4-AFC) paradigm, with always one segment including a target and 3 normal background segments. The percentage of correct responses (PC) was assessed based on 10 trials of each reader for each object type, size and imaging modality. Additionally, detection threshold diameters at 62.5 PC were assessed via non-linear regression fitting of the psychometric curve. The reproducibility study showed no significant differences in PC values. Evaluation of target detection in FFDM showed that microcalcification detection thresholds ranged between 110 and 118 µm and were similar compared to the detection in DBT (range of 106-158 µm). In DBT, detection of both mass types increased significantly (p = 0.0001 and p = 0.0002 for non-spiculated and spiculated masses respectively) compared to FFDM, achieving almost 100% detection for all spiculated mass diameters. In conclusion, a structured phantom with inserted targets was able to show evidence for detectability differences between FFDM and DBT modes for five commercial systems. This phantom has potential for application in task-based assessment at acceptance and commissioning testing of DBT systems.

Sclerosing Lymphocytic Lobulitis Mimicking a Tumor Relapse in a Young Woman with a History of Breast Cancer.

Sclerosing lymphocytic lobulitis or diabetic mastopathy is a benign entity with non-specific imaging features which can mimic breast carcinoma. It is a condition commonly associated with long standing diabetes and has also been linked with various auto-immune diseases. We present the case of a 27-year-old woman with a history of carcinoma of the left breast and otherwise unremarkable medical history, who developed sclerosing lymphocytic lobulitis in the right breast during follow-up.

Lactating Adenoma in the Presence of Galactoceles.

BACKGROUND: A 22-year-old woman was referred to our department with a painless, fast growing breast mass. She noticed this mass during lactation, after giving birth to her first child. Her gynecologist palpated a large mass in the left breast, two smaller nodules in the left breast, and one small nodule in the right breast. Ultrasonography of the breasts, mammography and MRI were performed, and a tentative diagnosis of phyllodes tumor was proposed. She was subsequently referred to our centre.

Breast cancer phenotype, nodal status and palpability may be useful in the detection of overdiagnosed screening-detected breast cancers.

BACKGROUND: Breast cancer remains the leading cause of female cancer death despite improvements in treatment and screening. Screening is often criticized for leading to overdiagnosis and overtreatment. However, few have attempted to identify overdiagnosed cases. PATIENTS AND METHODS: A large, consecutive series of patients treated for primary operable, screening-detected, breast cancer (n = 1610). Details from pathology and clinical reports, treatment and follow-up were available from our prospectively managed database. Univariate and multivariate Cox proportional models were used to study the prognostic variables in screening-detected breast cancers for distant metastatic and breast cancer-specific survival. RESULTS: We included 1610 patients. The mean/median follow-up was 6.0/6.0 years. Univariate analysis: tumor size, palpability, breast cancer phenotype and nodal status were predictors of distant metastasis and breast cancer-specific death. Multivariate analysis: palpability, breast cancer phenotype and nodal status remained independent prognostic variables. Palpability differed by breast cancer phenotype. CONCLUSION: Screening-detected breast cancer is associated with excellent outcome. Palpability, nodal status and breast cancer phenotype are independent prognostic variables that may select patients at increased risk for distant metastatic relapse and breast cancer-specific death. Overdiagnosed cases reside most likely in the nonpalpable node negative subgroup with a Luminal A phenotype.

Comparison of visual grading and free-response ROC analyses for assessment of image-processing algorithms in digital mammography.

OBJECTIVE: To compare two methods for assessment of image-processing algorithms in digital mammography: free-response receiver operating characteristic (FROC) for the specific task of microcalcification detection and visual grading analysis (VGA). METHODS: The FROC study was conducted prior to the VGA study reported here. 200 raw data files of low breast density (Breast Imaging-Reporting and Data System I-II) mammograms (Novation DR, Siemens, Germany)-100 of which abnormal-were processed by four image-processing algorithms: Raffaello (IMS, Bologna, Italy), Sigmoid (Sectra, Linköping, Sweden), and OpView v. 2 and v. 1 (Siemens, Erlangen, Germany). Four radiologists assessed the mammograms for the detection of microcalcifications. 8 months after the FROC study, a subset (200) of the 800 images was reinterpreted by the same radiologists, using the VGA methodology in a side-by-side approach. The VGA grading was based on noise, saturation, contrast, sharpness and confidence with the image in terms of normal structures. Ordinal logistic regression was applied; OpView v. 1 was the reference processing algorithm. RESULTS: In the FROC study all algorithms performed better than OpView v. 1. From the current VGA study and for confidence with the image, Sigmoid and Raffaello were significantly worse (p<0.001) than OpView v. 1; OpView v. 2 was significantly better (p=0.01). For the image quality criteria, results were mixed; Raffaello and Sigmoid for example were better than OpView v. 1 for sharpness and contrast (although not always significantly). CONCLUSION: VGA and FROC discordant results should be attributed to the different clinical task addressed. ADVANCES IN KNOWLEDGE: The method to use for image-processing assessment depends on the clinical task tested.

A rare presentation of breast cancer.

The case of a 67-year-old woman with a large lump in the left axillary region and the left breast is presented. Pathologic investigation of these masses in 2 hospitals was inconclusive. Further work-up in our radiologic department showed beside the presence of the two tumoral masses, abnormalities with the radiologic characteristics of granulomatous mastitis. Final pathologic analysis showed the presence of an invasive ductal carcinoma in the two masses in combination with a granulomatous stromal reaction.

Metastatic renal cell carcinoma presenting as a breast mass in a woman with history of primary breast cancer.

Metastatic extramammary breast tumours are uncommon and differential diagnosis with primary breast carcinoma may prove to be difficult. We report a case of a metastasis of a renal cell cancer in the breast in a woman with a history of primary breast cancer. On follow-up of her breast carcinoma, a lump was detected via mammography and ultrasound. Core needle biopsy revealed a metastatic extramammary lesion originating from an asymptomatic renal cell carcinoma. We conclude that the diagnosis of metastasis to the breast from extramammary tumours is important to avoid unnecessary surgery and insure proper treatment of the primary disease.

The relationship between the attenuation properties of breast microcalcifications and aluminum.

Screening mammography is one of the most challenging radiological techniques and this is partly due to the difficulty in detecting microcalcifications (MCs) against an anatomical background of varying mammographic tissue density. Further complicating factors in the detection of MCs include the small size and their resemblance to other bright structures in the breast. A number of different microcalcification simulating materials are available and these are often incorporated in test objects used to study some aspects of an imaging system, for example, optimal beam quality selection in digital mammography. Aluminum (Al) has similar x-ray attenuation properties to MCs and therefore Al is extensively used in test objects. However, to the best of our knowledge, the suitability of Al as a substitute material for MCs has not been studied explicitly. The aim of this study was therefore to demonstrate that spectral optimization studies for MCs can be performed with Al sheets. The approach used was twofold. First, contrasts generated by Al and MCs at several exposure settings were compared, and secondly an optimization study was performed with both Al and MCs as the contrasting target using an amorphous selenium (a-Se) based digital mammography unit. Specimens from stereotactic vacuum-assisted breast biopsies of non-palpable lesions with mammographic evidence of MCs were obtained from clinical routine patients. Contrasts generated by these MCs and by Al sheets were measured for Mo/Mo, Mo/Rh and W/Rh anode/filter combinations, for different polymethylmethacrylate (PMMA) thicknesses at the extremes of the x-ray tube voltages used clinically. A linear regression was then applied between the two measurements of contrast; the ratio of the angular coefficient q obtained from the fitted regression lines for Al and MCs ranged from 0.96 to 0.99 for Mo/Mo and Mo/Rh combinations at 2 and 4 cm PMMA, respectively, and from 0.83 at 4 cm PMMA to 1.14 at 7 cm PMMA for the W/Rh combination. For the optimization study, the signal-difference-to-noise ratio (SDNR) measured using the MCs was plotted as a function of mean glandular dose (MGD) for 4 cm PMMA, for the three different anode/filter combinations. The W/Rh combination always gave the highest SDNR for a given MGD. The SDNR and MGD were then used to define the common figure of merit SNR(2)/MGD; the setting that maximized this measure at 4 cm PMMA was 27 kV and a W/Rh combination. These results demonstrate a close correspondence between the attenuation properties of Al and extracted MC material over the energy range studied for the Mo/Mo, Mo/Rh and W/Rh anode/filter combinations. Furthermore, it was found that the exposure parameters that maximized the figure of merit for the MC specimen agree with results found in studies that used Al sheets as a substitute for the MC.

A quantitative method for evaluating the detectability of lesions in digital mammography.

This study presents a quantitative method for evaluating the detectability of microcalcifications in digital mammography. Four hundred and twenty microcalcifications (with various morphology, size and contrast), simulated with a previously validated method, were used for the creation of image datasets. Lesions were inserted into 163 regions of interests of 59 selected raw digital mammograms with various anatomical backgrounds and acquired with a Siemens Novation DR. After processing, these composite images were scored by experienced radiologists, who located multiple simulated lesions and rated them under conditions of free-search. For statistical analysis, free-response receiver-operating characteristic curves are plotted; the use of jackknife free-response receiver-operating characteristic method has also been investigated. The main advantage of this methodology is that the exact number of inserted microcalcifications is well known and that the lesions are fully characterised in terms of pathology, size, morphology and peak contrast. A first application has been the evaluation of the effect of anatomical background on microcalcifications detection. Preliminary findings in this study indicate that this method may be a promising tool to evaluate factors that have an influence on the detectability of lesions, such as the clinical processing or the viewing conditions.

Artifacts in digital mammography.

In April 2005 screening with digital mammography was allowed in the Flemish part of Belgium. A rigorous physical-technical Quality Control (QC) procedure based on the European guidelines (EUREF) was then implemented. Besides quality control, there is also quality assurance (QA). Detection of artifacts is part of the QA. During the central second reading, a continuous evaluation of the image quality is done. All visible artifacts in the digital images are registered and collected. All systems participate also in a daily quality control, with a daily exposure of a phantom image which is sent to the certified quality control group. The collected artifacts were divided into 5 different categories: patient related artifacts, technologist related artifacts, mammography unit related artifacts, processing related artifacts and viewing conditions related artifacts. Patient related artifacts are comparable with film screen mammography (FSM) and are therefore not discussed. One of the main artifacts in the group of technologist related artifacts is dust in the cassette of computed radiography (CR) systems. In the group of mammography unit related artifacts a distinction is made between the artifacts of CR systems and direct radiography (DR) systems. In the CR group, the artifacts originate in the reader, whereas in the DR group they originate in the detector, which in our study was a Selenium detector. Artifacts due to failure of the Selenium detector are most frequent in this last group. Processing related artifacts are found when the reading of the processing algorithm by the system or by the PACS software made mistakes. Because there is a daily quality control of the monitors of the soft copy work stations, we didn't recognize viewing conditions related artifacts. Some of the artifacts can simulate breast lesions or can disturb the reading of the images. In order to avoid misinterpretation, recognizing artifacts and understanding their physical-technical background are of great importance in digital breast imaging.

Evaluation of the diagnostic value of a computed radiography system by comparison of digital hard copy images with screen-film mammography: results of a prospective clinical trial.

The purpose of the study was to determine prospectively the diagnostic value of a computed radiography (CR) system by comparing mammographic hard copy images with screen-film mammography (SFM). A series of 100 patients, who came for diagnostic investigation, underwent two-view SFM (Lorad M-IV Platinum) and digital mammography with a CR system (AGFA CR system). The images were obtained by double exposure, i.e. same view without removing compression of the corresponding breast. The CR images were processed with dedicated processing for mammography. Six radiologists read sets of SFM and CR images. The primary efficacy parameter was the overall diagnostic value. The secondary efficacy parameters were lesion conspicuity and lesion details (for masses and micro-calcifications), tissue visibility at chest wall and at skin line, axillary details, overall density and sharpness impression and the overall noise impression. These parameters were scored by a 7-point scoring system. "CR non-inferior to SFM" was concluded if the lower confidence interval bound exceeded 80%. The confidence interval for the overall diagnostic value was between 96.4% and 100%. Pooled analysis of the ten features for image quality comparison demonstrated for all but one feature (lesion details of the calcifications) CR non-inferiority to SFM.

Amyloid deposition of the breast in primary Sjögren syndrome.

We report amyloid deposition in the breast presenting as suspicious microcalcifications on screening mammography. Stereotactic mammotome biopsy provided the diagnosis. The history of the patient revealed primary Sjögren syndrome. The combination of amyloid deposition in the breast and Sjögren's syndrome has only rarely been reported.

Current challenges of full field digital mammography.

Full field digital mammography (FFDM) has advantages over screen-film mammography (SFM), but some important challenges remain. The first challenge is related to the specific characteristics of FFDM. It remains unclear, which shape and limiting values of the modulation transfer function have the most influence on the performance of a detector, such as the effect of the image display on the overall image quality and the effect of processing on cancer detection. In order to assess the image quality of FFDM, we have set up a scoring system. The second challenge is related to screening mammography: is the quality of an image the same when it is viewed on different monitors and with different processing algorithms? Is Computer Aided Diagnosis necessary in a screening environment? In FFDM, the effect of different detectors, processing and display possibilities on the image and on cancer detection are not clearly investigated.

Image quality measurements and metrics in full field digital mammography: an overview.

This paper gives an overview of test procedures developed to assess the performance of full field digital mammography systems. We make a distinction between tests of the individual components of the imaging chain and global system tests. Most tests are not yet fully standardised. Where possible, we illustrate the test methodologies on a selenium flat-panel system.