Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants

Young breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR 12]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I\u2013III invasive early BC at age 6440 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P < 0.001). Median follow-up was 7.9 years. Second primary BC (P = 0.009) and non-BC malignancies (P = 0.02) were more frequent among mBRCA1 patients while distant recurrences were less frequent (P = 0.02). Irrespective of hormone receptor status, mBRCA1 patients had worse disease-free survival (DFS; adjusted HR = 0.76, 95% CI = 0.60\u20130.96), with no difference in distant recurrence-free interval (DRFI) and overall survival (OS). Patients with HR+ disease had more frequent distant recurrences (P < 0.001) and less frequent second primary malignancies (BC: P = 0.005; non-BC: P = 0.18). No differences in DFS and OS were observed according to hormone receptor status, with a tendency for worse DRFI (adjusted HR = 1.39, 95% CI = 0.94\u20132.05) in patients with HR+ BC. Type of mBRCA gene and hormone receptor status strongly impact BC clinical behavior and outcomes in mBRCA young patients. These results provide important information for patients\u2019 counseling on treatment, prevention, and surveillance strategies

The Return of the Mid-infrared to the VLT: News from the VISIR Upgrade

The VLT mid-infrared imager and spectrometer VISIR returns to science operations following an extended upgrade period. Among the most important modifications are: the imaging and spectroscopic detectors have been replaced with larger AQUARIUS (1024 by 1024 pixel) detector arrays; the N-band low-resolution grating has been exchanged; and support is now provided for precipitable water vapour monitoring, in order to select the best observing conditions. The AQUARIUS detectors stem from a development for very low background applications which result in excess noise under ground-based conditions. A series of interventions was needed to find a scheme that effectively exploits these detectors for ground-based use, involving the implementation of faster chopping. VISIR has been returned to service at the VLT with enhanced capabilities

Refinement of 1p36 Alterations Not Involving PRDM16 in Myeloid and Lymphoid Malignancies

Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups were identified: balanced translocations (N = 27) and telomeric rearrangements (N = 15), both mainly observed in myeloid disorders; and unbalanced non-telomeric rearrangements (N = 39), mainly observed in lymphoid proliferations and frequently associated with a highly complex karyotype. The 1p36 rearrangement was isolated in 12 cases, mainly myeloid disorders. The breakpoints on 1p36 were more widely distributed than previously reported, but with identifiable rare breakpoint cluster regions, such as the TP73 locus. We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1. We precised the common terminal 1p36 deletion, which has been suggested to have an adverse prognosis, in B-cell lymphomas [follicular lymphomas and diffuse large B-cell lymphomas with t(14;18)(q32;q21) as well as follicular lymphomas without t(14;18)]. Intrachromosomal telomeric repetitive sequences were detected in at least half the cases of telomeric rearrangements. It is unclear how the latter rearrangements occurred and whether they represent oncogenic events or result from chromosomal instability during oncogenesis

Simple scoring system to predict in-hospital mortality after surgery for infective endocarditis

BACKGROUND: Aspecific scoring systems are used to predict the risk of death postsurgery in patients with infective endocarditis (IE). The purpose of the present study was both to analyze the risk factors for in-hospital death, which complicates surgery for IE, and to create a mortality risk score based on the results of this analysis. METHODS AND RESULTS: Outcomes of 361 consecutive patients (mean age, 59.1\ub115.4 years) who had undergone surgery for IE in 8 European centers of cardiac surgery were recorded prospectively, and a risk factor analysis (multivariable logistic regression) for in-hospital death was performed. The discriminatory power of a new predictive scoring system was assessed with the receiver operating characteristic curve analysis. Score validation procedures were carried out. Fifty-six (15.5%) patients died postsurgery. BMI >27 kg/m2 (odds ratio [OR], 1.79; P=0.049), estimated glomerular filtration rate 55 mm Hg (OR, 1.78; P=0.032), and critical state (OR, 2.37; P=0.017) were independent predictors of in-hospital death. A scoring system was devised to predict in-hospital death postsurgery for IE (area under the receiver operating characteristic curve, 0.780; 95% CI, 0.734-0.822). The score performed better than 5 of 6 scoring systems for in-hospital death after cardiac surgery that were considered. CONCLUSIONS: A simple scoring system based on risk factors for in-hospital death was specifically created to predict mortality risk postsurgery in patients with IE

Impact of the line of treatment on progression-free survival in patients treated with T-DM1 for metastatic breast cancer.

Trastuzumab emtansine (T-DM1) is indicated as second-line treatment for human epidermal growth factor receptor 2 (HER2)-positive metastatic or unresectable locally advanced breast cancer, after progression on trastuzumab and a taxane-based chemotherapy. We wished to determine if the line of treatment in which T-DM1 is administered has an impact on progression-free survival (PFS) and in particular, if prior treatment with capecitabine/lapatinib or pertuzumab modifies PFS of further treatment with T-DM1. We performed a multicenter retrospective study in 3 Belgian institutions. We evaluated PFS with T-DM1 in patients treated for HER2 positive metastatic or locally advanced unresectable breast cancer between January 1, 2009 and December 31, 2016. We included 51 patients. The median PFS was 9.01 months. The line of treatment in which T-DM1 (1st line, 2nd line, 3rd line or 4+ lines) was administered had no influence on PFS (hazard ratio 0.979, CI95: 0.835-1.143). There was no significant difference in PFS whether or not patients had received prior treatment with capecitabine/lapatinib (9.17 vs 5.56 months, p-value 0.875). But, patients who received pertuzumab before T-DM1 tended to exhibit a shorter PFS (3.55 months for T-DM1 after pertuzumab vs 9.50 months for T-DM1 without pretreatment with pertuzumab), even if this difference was not statistically significant (p-value 0.144). Unlike with conventional chemotherapy, the line of treatment in which T-DM1 is administered does not influence PFS in our cohort of patients with advanced HER2-positive breast cancer

The Place of Extensive Surgery in Locoregional Recurrence and Limited Metastatic Disease of Breast Cancer: Preliminary Results

The aims of this study were first to clearly define two different entities: locoregional recurrences and limited metastatic disease and secondly to evaluate the place of extensive surgery in these two types of recurrence. Material and Methods. Twenty-four patients were followed from June 2004 until May 2014. All patients underwent surgery but for 1 patient this surgery was stopped because the tumour was unresectable. Results. The median interval between surgery for the primary tumour and the locoregional recurrence or metastatic evolution was 129 months. Eight patients had pure nodal recurrences, 4 had nodal and muscular recurrences, 5 had muscular + skin recurrences, and 8 had metastatic evolution. Currently, all patients are still alive but 2 have liver metastases. Disease free survival was measured at 2 years and extrapolated at 5 years and was 92% at these two time points. No difference was observed for young or older women; limited metastatic evolution and locoregional recurrence exhibited the same disease free survival. Conclusion. Extensive surgery has a place in locoregional and limited metastatic breast cancer recurrences but this option must absolutely be integrated in the multidisciplinary strategy of therapeutic options and needs to be planned with a curative intent

Assessment of potential process quality indicators for systemic treatment of breast cancer in Belgium: a population-based study.

Quality indicators (QIs) for the management of breast cancer (BC) have been published in Europe and internationally. In Belgium, a task force was established to select measurable process indicators of systemic treatment for BC, focusing on appropriateness of delivered care. The objective of this study was to evaluate the results of the selected QIs, both nationally and among individual centres. Female Belgian residents with unilateral primary invasive BC diagnosed between 2010 and 2014 were selected from the Belgian Cancer Registry database. The national number enabled linkage with the national reimbursement database, which contains information on all reimbursed medical procedures. A total of 12 process indicators were measured on the population and hospital level. Intercentre variability was assessed by median results and interquartile ranges. A total of 48  872 patients were included in the study. QIs concerning specific BC subtypes only applied to patients diagnosed in 2014 (n = 9855). Clinical stage (cStage) I patients (n = 17 116) were staged with positron emission tomography/computed tomography. Among patients who were pT1aN0 human epidermal growth factor receptor 2 (HER2) positive (n = 47), 25.5% (n = 12) received adjuvant trastuzumab. Among patients with de novo metastatic luminal A/B-like HER2-negative BC (n = 295), 17.3% (n = 51) received upfront chemotherapy. (Neo)adjuvant chemotherapy was administered in 52.4% (n = 12 592) of operated women with cStage I-III, in 37.0% (n = 1270) of operated women with cStage I-III luminal A/B-like HER2-negative BC, and in 19.1% of operated women with cStage I luminal A/B-like HER2-negative BC. In the population of operated patients with cStage I-III, of those younger than 70 years that started adjuvant endocrine therapy (n = 3591), 81.7% (n = 2932) continued treatment for ≥4.5 years. Among patients in cStage I-III older than 70 years (n = 8544), 19.0% (n = 1622) received (neo)adjuvant chemotherapy, whereas among patients with cStage I-III luminal A/B-like HER2-negative BC (n = 1388), 13.0% (n = 181) received (neo)adjuvant chemotherapy. In patients with cStage I-II luminal A/B-like HER2-negative BC older than 70 years (n = 1477), 11.6% (n = 171) were not operated and received upfront endocrine treatment. Well-considered QIs using population-based data can evaluate quality of care and expose disparities among treatment centres. Their use in daily practice should be implemented in all centres treating BC