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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. ispartof: ANNALS OF ONCOLOGY vol:33 issue:8 pages:769-785 ispartof: location:England status: published

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.

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.

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.

Background In patients with clinically lymph node negative (cN0) early breast cancer (EBC) treated with neoadjuvant chemotherapy (NACT), the sentinel lymph node biopsy (SLNB) can be performed before or after NACT. We report safety of axillary staging performing the SLNB prior to NACT in cN0 EBC and estimate NACT-induced downstaging to ypN0 in previously NACT-treated cN1 EBC, to make an assumption for avoiding axillary lymph node dissection (ALND) if SLNB was done after NACT. Patients and Methods Monocentric retrospective study of consecutive triple negative (TNBC) and HER-2 amplified BC patients treated with standard NACT. cN0 patients had SLNB before NACT followed by local therapy. Axillary lymph node dissection (ALND) post-NACT was performed in all cN1 and in cN0 cases with a positive or failed SLNB. Using descriptive statistics, we here report SLNB-detection and SLNB-positive rate, SLNB-operative complications, complete tumor regression in the breast (ypT0/is) and disease-free survival (DFS) for cN0 cases and NACT-induced downstaging to ypN0 in previously NACT-treated cN1 EBC. Results We included 245 NACT-treated patients; 119 cN0 and 126 cN1. SLNB-detection rate in cN0 cases was 99,2%; 25 or 21% had ≥ 1 involved SLN, 21.8% experienced SLNB related-complications (e.g. infection, seroma, hematoma) leading to NACT-delay in 3 and interruption in 1 patient. Median start of NACT after SLNB was 7 days (range 1-20 days). In patients with a positive SLNB, there were no additional involved nodes in the ALND. In 5 of these patients, therapy response in a lymph node was described. Complete tumor regression in the breast (ypT0/is) was 52% in SLNB-positive and 59,1% in SLNB-negative cN0 cases. NACT-induced ypN0 was 61% in cN1 cases. At 30 months of median follow-up (range 1-86 months), DFS was 93,2% (4.2% metastatic; no axillary relapse) in cN0 cases. Median DFS was better for patients with complete tumor regression in the breast as compared to those with partial response; 95.6% and 90% respectively. Conclusion In conclusion, performing SLNB before NACT in cN0 cases is a safe and accurate method. While some pN1(sn) could have avoid ALND by NACT-induced axillary down-staging, based on our assumption, long term follow-up is needed to conclude whether SLNB after NACT is safe. Keywords: Breast cancer, neoadjuvant chemotherapy, timing sentinel lymph node biopsy Citation Format: Delameilleure M, Smeets A, Nevelsteen I, Han S, Van Nieuwenhuysen E, Berteloot P, Hoste G, Salihi R, Van Ongeval C, Keupers M, Prevos R, Wildiers H, Punie K, Van Limbergen E, Weltens C, Janssen H, Floris G, Vergote I, Neven P. Monocentric experience with the sentinel lymph node biopsy prior to neoadjuvant chemotherapy in clinically lymph node negative early breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-32.

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.

Background: Histologic grade 2 breast cancer may benefit most from molecular classification for prognosis. We studied the prognostic value of ‘detection mode’ and ‘palpability’ together with other prognostic variables in a consecutive series of grade 2 lesions. Patients and methods: We used follow-up data from new diagnosed and primary operable grade 2 breast cancers from UH Leuven (January 2000 - May 2005). Endocrine, chemo-and radiotherapy were given when indicated. The first appearing breast cancer related event (BCRE) was calculated as local (local, regional or contra-lateral) or metastatic (metastatic if both appeared together). These prognostic variables were assessed: age at diagnosis (per decade increase), tumor size (per cm increase), screening (yes/no), palpability (yes/no), lobular type (yes/no), chemotherapy (yes/no), endocrine therapy (yes/no), lymph node status (0, 1, 2-4, >4), combined expression of IHC-measured ER (pos = any expression), PgR (pos if any expression) and HER-2 (positive = IHC2/3+ and FISH pos), architectural, nuclear and mitotic score. Univariable and multivariable proportional hazards Cox regression using the Firth's penalization method to reduce bias in the parameter estimates were used. Results: Of the 1013 patients in the dataset, 14 had missing values (1.4%). With a median follow-up of 80 months, we observed 116 BCRE (11.6%); 43 local and 73 metastatic. In univariable analysis, screen detected cancers showed better (HR 0.63, 95% CI 0.42-0.93) and palpable cancers worse prognosis (HR 1.96, 95% CI 1.13-3.71) than non-screen detected and non-palpable cases respectively. The beneficial univariable effect of screening weakened in the multivariable analysis (HR 0.83, 95% CI 0.52-1.31) as 582/602 (97%) of non-screen detected cancers were palpable vs 227/397 (57%) for screen-detected cancers. If palpable was omitted from the multivariable model the HR of screening decreased to 0.68 (95% CI 0.44-1.03) thereby approximating its univariable result. Conclusion: Overall, palpability is more strongly related to prognosis, but detection method also has an effect even though we do not have enough events to show this with a convincing level of reliability. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-08-09.

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.

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.

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.

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.

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.

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).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.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 (p0.001) 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).VGA and FROC discordant results should be attributed to the different clinical task addressed.The method to use for image-processing assessment depends on the clinical task tested.

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 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.

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.

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.

MRI of the breast has proved its role in the diagnosis of breast cancer. Despite the amount of studies with MRI, the technique has not been standardised yet. This is one of the reasons for the huge difference in specificity the reported in the different studies (from 30% to 95%). Because the many pitfalls of the technique, the specificity of MRI of the breast is correlated to the experience of the investigator. When the established indications are respected, specificity increases. Presently accepted indications are: differentiation between postoperative fibrosis and tumor recurrence, multifocality or contralateral breast carcinoma, evaluation of prosthesis, discrepancy between the different diagnostic techniques, high risk patients with dense breasts. Less frequently but nevertheless a good indication is proven axillary lymph node metastases from an unknown primary tumor. Microcalcifications still are not a good indication for MRI of the breast. MRI is still inferior to mammography in detecting ductal in-situ carcinoma or very small carcinomas because the neo-angiogenesis of these tumors is too faint to be detected by contrast-enhanced MRI. MRI instead of mammography or to solve a problem resulting from a bad mammographical examination is certainly not advised. New sequences, including diffusion and perfusion, and new contrast agents are keenly awaited.

A case of idiopathic granulomatous mastitis mimicking breast carcinoma clinically and radiographically is reported with mammography, sonography and MR images.

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.

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.

Background In histological grade 2 BC molecular classification is of high value (JNCI 2006; 98:262), but clinical, pathological and immunohistochemical variables may be useful as well. We here assess the prognostic value of ‘mode of detection’ and ‘palpability’ in grade 2 BC. Patients and methods The disease free interval in all primary operable grade 2 BC from UZ Leuven (01/2000 – 05/2005) was studied. Patients with missing variables (n = 17) were excluded. Univariable and multivariable proportional hazards Cox regression using the Firth's penalization method to reduce bias in the parameter estimates were used. The assessed prognostic variables were age at diagnosis, tumor size, nodal status, BC subtype, method of detection, lobular versus other histology, systemic adjuvant therapy, nuclear grade, architectural grade, mitotic count. Estimated hazard rates (HR) are presented (only for significant variables, see table). Results 1010 patients were included. Median follow-up: 7 years 10 months. 144 events (14.3%) were observed: 52 local and 92 metastatic. In univariable analysis and compared with palpable non-screen detected BC, HR for relapse was 0.34 (95% CI 0.17-0.62) for screen detected not palpable and 0.75 (95% CI 0.49-1.12) for screen detected palpable BC. The beneficial univariable effect of ‘screen detected not palpable’ remained in the multivariable analysis, together with significant prognostic value for lymph node status and BC subtype (see Table 1 ). Table 1 . Multivariable proportional hazards Cox regression Variable HR (95% CI) Positive lymph nodes 0 Reference 1 1.11 (0.63,1.86) 2-4 1.66 (0.97,2.75) >4 3.32 (1.83, 5.85) * NNP vs other 5.63 (1.90, 14.2) Screen and Palpable Non screen - Palpable Reference Screen – Not palpable 0.38 (0.19, 0.70) Screen - Palpable 0.87 (0.56, 1.33) * ER-negative, PgR-negative, HER-2 positive Conclusion Screen-detected not-palpable BCs were found to be independently associated with a better disease free interval among women with a primary operable grade 2 invasive BC. Method of detection should be taken into account when estimating prognosis in early BC. Disclosure All authors have declared no conflicts of interest.

Introduction Mammographic screening has shown to reduce BC mortality, but approximately 30% of the mortality reduction remains unexplained. Method of detection has independent prognostic value and we here assess its value in function of BC phenotypes. Patients and methods Primary operable invasive BC patients treated at the Multidisciplinary BC Centre UZ-Leuven (01/2000 – 12/2009) were included. Preoperative systemic therapy (n = 407), metastases at diagnosis (n = 228), male patients (n = 28) or external surgery (n = 530) were exclusion criteria. Details on treatment and pathology are described in detail elsewhere (Brouckaert et al., Breast Cancer Res Treat., 2009 May; 115(2): 349-58). BCs were allocated to screen detected (n = 1610) when diagnosed through organized or opportunistic screening (missing n = 91) and to palpable when palpable by the treating physician (missing n = 57). We defined BC phenotypes as Luminal A (ER and/or PR positive HER2 negative, grade 1/2), Luminal B1 (idem, grade 3), Luminal B2 (ER and/or PR and HER-2 positive), HER-2 like (ER/PR negative, HER-2 positive) and Triple negative (2011 St. Gallen criteria). Multivariable Cox proportional hazard models were used adjusting for age, size, grade, nodal status, ER, PR and HER2 receptor status and adjuvant therapy (see Table 1 ). The proportional hazard assumption for the Cox model was evaluated by including time-dependent covariates in the models, which were included when significant. Results Median follow-up 6.1 years. Table 1 . Adjusted HR (Screening versus non-) Distant metastasis free survival (p-value) Breast cancer specific survival (p-value) All (n = 4227) 0.42 (0.03) 0.49 (0.13) Luminal A (n = 2338) 0.79 (0.29) 0.63 (0.2) Luminal B1 (n = 924) 0.58 (0.03) 0.69 (0.23) Luminal B2 (n = 289) 0.37 (0.07) 0.53 (0.39) HER-2 like (n = 173) 0.39 (0.09) 0.46 (0.24) Triple negative (n = 412) 0.44 (0.04) 0.23 (0.01) Conclusion BC screening may be criticized to reduce mortality by simply diagnosing indolent tumors (length bias). However, the prognostic value of method of detection seems to have increasing value in increasingly more aggressive BC phenotypes. Method of detection may also prove to be a new and independent prognostic tool to assess outcome in triple negative BC. References on demand. Disclosure All authors have declared no conflicts of interest.

Gene expression studies on breast cancer have generally been performed on tissue obtained at the time of surgery. Overexpression of several genes may be a result of surgical trauma or preoperative manipulation, such as the injection of radioactive substance to examine spread of cancer cells (sentinel node), and may not reflect any biological impact of the disease. In this study we have compared the gene expression profiles in preoperative tissue (core needle biopsies) while tumor is still in its normal milieu to postoperative tissue from the same tumor obtained during surgery. Fifteen patients were included of which 12 had undergone sentinel node diagnosis procedure before operation. Gene expression and miRNA microarray analysis were performed using total RNA from all the samples. Paired significance analysis of microarrays revealed 228 differently expressed genes, including several early response stress-related genes such as members of the fos and jun cancer. Only two miRNAs, miR-923 and miR-1274b, were differentially expressed. These results were confirmed by large-scale expression signature analysis, which showed stability of most breast cancer specific expression signatures, while signatures related to immune response and stress response scored differently on pre- and postoperative samples. The expression profiles of preoperative breast cancer tumors differ from those of postoperative tumors for a small fraction of genes (228 out of approx. 18 000). However, the expression of these genes in concert affects specific biological pathways, which may relate to stress responses in the tissue. The results highlight the necessity of having in mind that some of the expression profiles found in the analyses of breast cancer tissue may simply be result of differences in the surgical trauma and timing of when samples are taken, and not necessarily associated with tumor biology. Disclosure All authors have declared no conflicts of interest.

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.

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.

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.

The ventricle-brain ratio (VBR) of 42 chronic schizophrenic patients was compared with that of 42 age-matched medical controls. For the schizophrenics, the relationship of various clinical parameters to the VBR was assessed, and the outcome of 12 weeks of double-blind treatment with either risperidone or haloperidol. The results confirm that schizophrenic patients have slightly enlarged lateral ventricles compared with medical controls. Only for schizophrenics, an effect of age, but not of duration of illness, was noticed. This study does not support the validity of a clinical subdivision of chronic schizophrenic patients on the basis of the VBR. Neither negative, positive nor general psychopathological symptoms, as measured by the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), were related to the VBR, nor were abnormal involuntary movements or extrapyramidal symptoms. No association between season of birth or a family history of major mental disorder and VBR could be demonstrated. Treatment response was predicted by the total PANSS score and the PANSS general psychopathology subscale score at baseline. There was a trend for patients with higher VBR to have a more favourable treatment outcome, independent of the treatment (risperidone or haloperidol).

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.