Citations

Abstract Introduction. Male breast cancer (male BC) is a rare disease for which disease management is extrapolated from females. IMBC, an international consortium, which previously reported on clinico-pathological aspects, now reports on molecular subgroups revealed by RNA sequencing and their relation to patient outcome. Methods. Tumor samples from the retrospective MALE BC registry diagnosed between 1990-2010 and with pathology and outcome data (relapse-free- (RFS) and overall survival (OS)) were included (n=699). To allow the discovery of prognostic features, we selected, stratified for known risk factors (TN stage, grade, age at diagnose and adjuvant endocrine treatment), from the cohort 152 cases with poor (RFS <= 4 yrs) and good outcome (RFS > 7yrs) evenly distributed. Here, we report RNA sequencing results of the first 73 cases, 38 with poor and 35 with good outcome. RNA sequencing reads were used to generate gene expression values and to report transcripts carrying driver mutations. Unsupervised clustering identified subgroups and within subgroups differentially expressed genes were identified. The reported prognostic male BC subgroups M1 and M2 (Johansson BCR 2012(14):R31) were also annotated. All identified subgroups were related to outcome using logistic regression (p-value using Wald test). Results. Unsupervised clustering revealed 2 main subgroups of which group 1 was enriched for expression of ER target genes, WNT3 and genes from amplicons known for female BC, e.g. 19p13 (CCNE1), 8q24 (MYC), and 11q13 (CCND1). The biology of the smaller group 2 was less defined but TGFβ2 expression was high as were various kallikreins (KLK) including interestingly KLK3 (prostate specific antigen). Other known amplified regions [(8p11 (FGFR1), 20q13 (ZNF217) and 12q15 (MDM2)] and mutated transcripts [PIK3CA (H1047R/L/Q; E542K, E545K, N345K; 16% of cases), TP53 and SF3B1 (K700E) (2% of cases)] were identified. Profound tumor infiltrate gene expression was present in 5% of cases and one third of cases expressed proliferation markers. Except for TP53, none of these latter characteristics were unevenly distributed among the 2 main subgroups. ER and AR were highly correlated, particularly in group 1. The two main groups could be further subdivided. Group 1 comprised 3 subgroups of which subgroup 1a expressed TFF1/3 and NAT1, well-known ER targets, while subgroups 1b and 1c expressed other ER targets,respectively BEX1 and PITX1. HOXC cluster expression differentiated subgroup 1b from 1a and 1c. None of these intrinsic subgroups were, however, related to RFS. The previously reported M2 subgroup, which largely segregated with subclusters 1a and 1b, was associated with a better RFS than the M1 subgroup (OR=2.9; 95%CI 1.1-7.5; p-value=0.03). Conclusions. 1) Intrinsic subtypes of male BC were revealed and their subgrouping is defined by ER associated subsets of genes. 2) The association of the reported M2 subgroup of male BC with longer RFS was validated; 3) Currently identified biological characteristics of male BC may improve future treatments. The full report on 152 cases including a comparison to female BC will be presented at the conference. This research was funded by Breast Cancer Research Foundation Citation Format: Martens JWM, Sieuwerts A, Ponchet C, Smid M, de Weerd V, Slaets L, Piper T, van Deurzen CHM, Schroder CP, Stangle C, Kloosterman W, van Leeuwen-Stok E, Nilsson C, Vermeij J, Peeters S, Goulioti T, Nowaczyk M, Aebi S, Rubio IT, Kelly C, Bayani J, Porter P, Murray M, Hudis C, Middleton L, Korde L, Ruddy K, Winer E, Bogler O, van den Weyngaert D, dal Lago L, Fraser J, Benstead K, van Asperen C, Linderholm B, Hedenfalk I, Tryfonidis K, Giordano S, Bartlett J, Cardoso F. Molecular subtyping of male breast cancer by the International male breast cancer program (IMBC): EORTC 10085/TBCRC 0-29/BIG 2-07/NABCG/BOOG 2009-04 [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD7-12.

AbstractInjury to the posterolateral corner (PLC) of the knee can lead to both varus and rotational instability. Multiple PLC reconstruction techniques have been described, including one-tailed graft (fibula-based constructs) or two-tailed graft (combined fibula- and tibia-based constructs). The purpose of our study was to evaluate the clinical outcomes of anatomical two-tailed graft reconstruction of the PLC in the setting of multiligament knee injuries (MKLIs) with grade III varus instability. Patients were identified through a prospective MLKI database between 2004 and 2013. Patients who received fibular collateral ligament and PLC reconstructions using a two-tailed graft and had a minimum follow-up of 2 years were included. Patients were assessed for clinical laxity grade, range of motion, and functional outcomes using Lysholm and International Knee Documentation Committee (IKDC) scores. Twenty patients (16 male, 4 female) with a mean age of 30.7 (range: 16–52) and a mean follow-up of 52.2 months (range: 24–93 months) were included. Knee dislocation (KD) grades included: 4 KD-1, 10 KD 3-L, 5 KD-4, and 1 KD-5. No patients had isolated PLC injuries. Mean IKDC and Lysholm score were 73.1 ± 25.8 and 78 ± 26, respectively. Mean range of motion was –1.1 to 122.8. In full extension, two patients (10%) had grade 1 laxity to varus stress. In 30 degrees of knee flexion, five (25%) patients had grade 1 laxity, and two (10%) had grade 2 laxity. Anatomical two-tailed PLC reconstruction can reliably restore varus stability when performed on patients with MLKIs and type C posterolateral instability with hyperextension external rotation recurvatum deformity. Satisfactory functional outcome scores were achieved in the majority of patients. This study supports the use of an anatomical two-tailed PLC reconstruction in the multiligament injured knee. The level of evidence is IV, case series.

Objective A gluten-free diet is the only treatment option of coeliac disease, but recently an increasing number of trials have begun to explore alternative treatment strategies. We aimed to review the literature on coeliac disease therapeutic trials and issue recommendations for outcome measures. Design Based on a literature review of 10 062 references, we (17 researchers and 2 patient representatives from 10 countries) reviewed the use and suitability of both clinical and non-clinical outcome measures. We then made expert-based recommendations for use of these outcomes in coeliac disease trials and identified areas where research is needed. Results We comment on the use of histology, serology, clinical outcome assessment (including patient-reported outcomes), quality of life and immunological tools including gluten immunogenic peptides for trials in coeliac disease. Conclusion Careful evaluation and reporting of outcome measures will increase transparency and comparability of coeliac disease therapeutic trials, and will benefit patients, healthcare and the pharmaceutical industry.

AbstractIntroductionMedial temporal lobe (MTL) uptake on tau–positron emission tomography (PET) is seen not only in Alzheimer's disease (AD) dementia but also in the aging population. The relationship of these findings to the development of AD dementia needs to be better understood.MethodsTau‐PET with AV‐1451 was performed on 576 cognitively unimpaired (CU) participants aged 50–94 years. The number of CUs with and without abnormal MTL regions and those with or without extra‐MTL abnormalities was determined. Left and right regions were compared within each subject.ResultsOf CUs, 58% (334/576) had abnormal tau‐PET findings. MTL abnormalities were present in 41% (238/576) of subjects.DiscussionMTL tau‐PET signal is often associated with abnormal extra‐MTL tau‐PET signal in CU participants and may represent neurofibrillary tangle development that could identify participants most likely to develop AD dementia. Tau‐PET signal exclusively outside of the MTL is seen in 17% of CU participants and could be the initial findings in participants in different AD dementia pathways. Significant (P < .001) differences in tau–standardized uptake value ratio between sides were noted in 26 of 41 examined brain regions implicating further study of side‐specific deficits.

Background: Patellar height has long been considered a risk factor for patellofemoral instability. However, recent pediatric literature demonstrated a reduction in patellar height measurements following medial patellofemoral ligament (MPFL) reconstruction. Purpose: To assess the mean change in patellar height and the percentage of skeletally mature patients with patellar height ratios reduced to within-normal limits following MPFL reconstruction. Study Design: Case series; Level of evidence, 4. Methods: Adult patients undergoing primary MPFL reconstruction for recurrent lateral patellar instability between 2005 and 2013 were identified. Pre- and postoperative (within 1 year of surgery) lateral knee radiographs were assessed for patellar height indices, including Caton-Deschamps, Blackburne-Peel, and Insall-Salvati ratios. The change in patellar height and the number of patients reduced from abnormal to normal patellar height ratios following MPFL reconstruction were assessed. Results: Overall, 32 adult patients were included in the study, with a mean age of 25.7 years (range, 18-55 years). There were 21 women (66%) and 11 men (34%). Insall-Salvati, Blackburne-Peel, and Caton-Deschamps ratios all demonstrated significant reductions in patellar height between pre- and postoperative lateral knee radiographs ( P < .001). All 3 indices showed a reduction in the number of patients meeting the criteria for patella alta following MPFL reconstruction. A total of 64% of patients had an abnormal preoperative Caton-Deschamps ratio reduced to within normal limits postoperatively. Conclusion: MPFL reconstruction provides a consistent reduction in patellar height measurements. The Caton-Deschamps ratio was reduced to the reference range following MPFL reconstruction in 64% of patients with preoperative patella alta. Surgeons treating patellofemoral instability should expect a reduction in patellar height after ligament reconstruction, which may affect the need for more invasive distalization procedures.

AbstractThe relationship between clinicopathologic diagnosis and 123I‐FP‐CIT SPECT in 18 patients with dementia (12 with Lewy body disease) from one center in the United States was assessed. The sensitivity and specificity of abnormal 123I‐FP‐CIT SPECT with reduced striatal uptake on visual inspection for predicting Lewy body disease were 91.7% and 83.3%, respectively. The mean calculated putamen to occipital ratio (mPOR) based on regions of interest was significantly reduced in Lewy body disease compared to non‐Lewy body disease cases (P = 0.002). In this study, abnormal 123I‐FP‐CIT SPECT was strongly associated with underlying Lewy body disease pathology, supporting the utility of 123I‐FP‐CIT SPECT in the clinical diagnosis of dementia with Lewy bodies.