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.

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.

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.

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.

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.

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.

NMR imaging study of the pharmacodynamics of polylysine-gadolinium-DTPA in the rabbit and the rat.

The pharmacodynamics of polylysine-(Gd-DTPA) (Schering, Berlin, Germany), a new blood pooling contrast agent for MRI, were studied in the rabbit and the rat. Polylysine-(Gd-DTPA) is a compound with high LD50. Due to its high molecular weight (50.000) and physico-chemical properties, it remains in the vascular system; during the first hour, the plasma level is three times higher than for Gd-DTPA. MRI was performed at 1.5 T using a SE sequence with TR/TE = 300/15 or 20 msec. Signal intensities of muscle, liver and kidney were measured before and after intravenous injection of the contrast agent (0.1 mmol/kg) during 8 hours in the rat (n = 3) and up to 2 wk in the rabbit (n = 3). A dose response study in three additional rabbits confirmed that the 0.1 mmol/kg dose was optimal. The pharmacodynamics results show that the effects of polylysine-(Gd-DTPA) are similar in both the rabbit and the rat. The liver signal is enhanced by about 60% immediately after injection in both species. This enhanced signal decays to half its maximal value in about one hour, which makes the contrast agent useful for clinical applications at a dose of 0.1 mmol/kg. In the kidney medulla and cortex the signals are enhanced by much larger factors (about 3 to 4); it takes at least one day for the kidney to clear the contrast agent in both species.

MR imaging of spondylitis with gadopentetate dimeglumine enhancement.

MR images of 17 patients with spondylitis were reviewed. T1 weighted spin-echo scans were obtained in 17 patients and proton density and T2 weighted scans were obtained in 15 patients. Unenhanced and gadopentetate dimeglumine enhanced scans were obtained in all patients. Five patients had pyogenic spondylitis, two patients tuberculous spondylitis, two patients fungal spondylitis and eight patients postoperative spondylitis. The four criteria described by Thrush and Enzmann were generally applicable in our study: 1) narrowing of the intervertebral disc; 2) cortical bone erosion; 3) abnormal signal in the adjacent vertebral bodies and 4) abnormal paraspinous or epidural soft tissue. In addition to plain sagittal T1 and T2 weighted images we suggest the routine administration of gadopentetate dimeglumine to assess the extent of the soft tissue mass and to differentiate postoperative spondylitis from a normal postoperative course, by showing disc enhancement. Disc enhancement occurs infrequently in the normal postoperative course. If it is associated with adjacent vertebral bone marrow changes it should be considered as postoperative spondylitis. A differential diagnosis between pyogenic, tuberculous, fungal and postoperative spondylitis was not possible although the pattern of enhancement in tuberculous spondylitis was different from the other cases of spondylitis.

[Mammographic symptomatology of malignant breast lesions]. / Mammografische semeiologie van de maligne borstletsels.

Malignant breast images may include opacities (stellar--rounded with blurred margins), microcalcifications, opacities with microcalcifications, asymmetric fibroglandular tissue, or distortion of the mammographic pattern. Secondary signs may also be present, such as skin thickening, skin or nipple retraction, prominent vascularisation, axillary lymph nodes. The aim of this paper is to describe the different aspects and to make the differential diagnosis from benign tumors and normal tissue.

[Galactography]. / Galactografie.

Spontaneous single duct discharge is the main indication for galactography. This abnormality has in most cases a benign aetiology (> 90%). With a meticulous technique and sufficient experience, the ducts can be cannulated in 95% of the cases. A nipple adenoma with a blood stained discharge is seldom to pass for cannulation. Because cytology of the nipple discharge is not always positive in case of intraductal proliferations, microdochectomy must be used to obtain the differential diagnosis. Galactography shows multiple normal duct variations, depending on age, surrounding tissue, and a possible history of lactation. Pathologic images can be seen in dystrophic breasts, solitary papillomas, (juvenile) papillomas or (intraductal) carcinomas. In addition to high frequency ultrasonography (> or = 10 MHz), which is able to visualise the retro-areolar and superficial ducts, galactography can give a more detailed and better overview of the pathology.

Parosteal osteosarcoma.

A case of parosteal osteosarcoma is reported. In spite of the pathognomonic plain radiographic signs of parosteal osteosarcoma, it is very uneasy to differentiate it from myositis ossificans circumscripta in the mature stage. CT and MRI defined the extent of the tumor into the soft tissue, the medullary and cortical invasion and gave more information about the composition of the lesion.

Adamantinoma of the tibia: MRI documentation.

We report two cases of adamantinoma of the tibia, for which an MR examination was performed. Each patient was initially investigated with plain radiography and in case 2, a computerized tomography was also performed. The MR characteristics of this tumor are scarcely documented in the even few case reports of this tumor. MRI does not add to the (differential) diagnosis but does have significance in the preoperative staging because it allows adequate delineation of tumor, which is essential for a complete and curative resection of the tumor.

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.