Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline

PURPOSE: To develop guideline recommendations concerning optimal neoadjuvant therapy for breast cancer. METHODS: ASCO convened an Expert Panel to conduct a systematic review of the literature on neoadjuvant therapy for breast cancer and provide recommended care options. RESULTS: A total of 41 articles met eligibility criteria and form the evidentiary basis for the guideline recommendations. RECOMMENDATIONS: Patients undergoing neoadjuvant therapy should be managed by a multidisciplinary care team. Appropriate candidates for neoadjuvant therapy include patients with inflammatory breast cancer and those in whom residual disease may prompt a change in therapy. Neoadjuvant therapy can also be used to reduce the extent of local therapy or reduce delays in initiating therapy. Although tumor histology, grade, stage, and estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) expression should routinely be used to guide clinical decisions, there is insufficient evidence to support the use of other markers or genomic profiles. Patients with triple-negative breast cancer (TNBC) who have clinically node-positive and/or at least T1c disease should be offered an anthracycline- and taxane-containing regimen; those with cT1a or cT1bN0 TNBC should not routinely be offered neoadjuvant therapy. Carboplatin may be offered to patients with TNBC to increase pathologic complete response. There is currently insufficient evidence to support adding immune checkpoint inhibitors to standard chemotherapy. In patients with hormone receptor (HR)-positive (HR-positive), HER2-negative tumors, neoadjuvant chemotherapy can be used when a treatment decision can be made without surgical information. Among postmenopausal patients with HR-positive, HER2-negative disease, hormone therapy can be used to downstage disease. Patients with node-positive or high-risk node-negative, HER2-positive disease should be offered neoadjuvant therapy in combination with anti-HER2-positive therapy. Patients with T1aN0 and T1bN0, HER2-positive disease should not be routinely offered neoadjuvant therapy.Additional information is available at www.asco.org/breast-cancer-guidelines

Spectroscopy of 91Zr51 at medium to high spins

Identification of near-yrast states in the β-stable nucleus 91Zr51 has been carried out using the fusion evaporation reaction, 82Se(13C,4n)91Zr at an incident beam energy of 50 MeV. States above the reported r = 6 μs, Iπ = 21/2+ isomeric level at Ex = 3167 keV have been identified for the first time in this work, a tentative decay scheme of near-yrast states to excitation energies in excess of 10 MeV has been constructed. These states are of relevance to shell model structures formed via limited valence-space configurations in this semi-magic N = 51 nucleus

Association between acute respiratory disease events and the MUC5B promoter polymorphism in smokers

A single-nucleotide polymorphism (rs35705950) in the mucin 5B (MUC5B) gene promoter is associated with pulmonary fibrosis and interstitial features on chest CT but may also have beneficial effects. In non-Hispanic whites in the COPDGene cohort with interstitial features (n=454), the MUC5B promoter polymorphism was associated with a 61% lower odds of a prospectively reported acute respiratory disease event (P=0.001), a longer time-to-first event (HR=0.57; P=0.006) and 40% fewer events (P=0.016). The MUC5B promoter polymorphism may have a beneficial effect on the risk of acute respiratory disease events in smokers with interstitial CT features

Fast-timing measurements in neutron-rich odd-mass zirconium isotopes using LaBr3:Ce detectors coupled with Gammasphere

A fast-timing experiment was performed at the Argonne National Laboratory to measure the lifetimes of the lowest lying states of nuclei belonging to the deformed regions around mass number A 110 and A 150. These regions were populated via spontaneous fission of 252 Cf and the gamma radiation following the decay of excited states in the fission fragments was measured using 51 Gammasphere detectors coupled with 25 LaBr 3 :Ce detectors. A brief description of the acquisition system and some preliminary results from the fast-timing analysis of the fission fragment 100Zr are presented. The lifetime value of \u3c4 = 840(65) ps was found for the 2 + state in 100 Zr consistent within one standard deviation of the adopted value with 791 +26 -35 ps. This is associated with a quadrupole deformation parameter of 0.36(2) which is within one standard deviation of the literature value of 0.3556 +82 -57

Fast-timing measurements in the ground-state band of Pd114

Using a hybrid Gammasphere array coupled to 25 LaBr3(Ce) detectors, the lifetimes of the first three levels of the yrast band in Pd-114, populated via Cf-252 decay, have been measured. The measured lifetimes are tau(2+) = 103(10) ps, tau(4+) = 22(13) ps, and tau(6+) <= 10 ps for the 2(1)(+), 4(1)(+), and 6(1)(+) levels, respectively. Palladium-114 was predicted to be the most deformed isotope of its isotopic chain, and spectroscopic studies have suggested it might also be a candidate nucleus for low-spin stable triaxiality. From the lifetimes measured in this work, reduced transition probabilities B(E2; J -> J - 2) are calculated and compared with interacting boson model, projected shell model, and collective model calculations from the literature. The experimental ratio R-B(E2) = B(E2; 4(1)(+) -> 2(1)(+))/B(E2; 2(1)(+) -> 0(1)(+)) = 0.80(42) is measured for the first time in Pd-114 and compared with the known values R-B(E2) in the palladium isotopic chain: the systematics suggest that, for N = 68, a transition from gamma-unstable to a more rigid gamma-deformed nuclear shape occurs

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Fast-timing measurements in the ground-state band of Pd 114

Using a hybrid Gammasphere array coupled to 25 LaBr3(Ce) detectors, the lifetimes of the first three levels of the yrast band in Pd114, populated via Cf252 decay, have been measured. The measured lifetimes are τ2+=103(10)ps, τ4+=22(13)ps, and τ6+≤10ps for the 21+, 41+, and 61+ levels, respectively. Palladium-114 was predicted to be the most deformed isotope of its isotopic chain, and spectroscopic studies have suggested it might also be a candidate nucleus for low-spin stable triaxiality. From the lifetimes measured in this work, reduced transition probabilities B(E2;J→J-2) are calculated and compared with interacting boson model, projected shell model, and collective model calculations from the literature. The experimental ratio RB(E2)=B(E2;41+→21+)/B(E2;21+→01+)=0.80(42) is measured for the first time in Pd114 and compared with the known values RB(E2) in the palladium isotopic chain: the systematics suggest that, for N=68, a transition from γ-unstable to a more rigid γ-deformed nuclear shape occurs

The Value of Rare Genetic Variation in the Prediction of Common Obesity in European Ancestry Populations

Polygenic risk scores (PRSs) aggregate the effects of genetic variants across the genome and are used to predict risk of complex diseases, such as obesity. Current PRSs only include common variants (minor allele frequency (MAF) ≥1%), whereas the contribution of rare variants in PRSs to predict disease remains unknown. Here, we examine whether augmenting the standard common variant PRS (PRScommon) with a rare variant PRS (PRSrare) improves prediction of obesity. We used genome-wide genotyped and imputed data on 451,145 European-ancestry participants of the UK Biobank, as well as whole exome sequencing (WES) data on 184,385 participants. We performed single variant analyses (for both common and rare variants) and gene-based analyses (for rare variants) for association with BMI (kg/m2), obesity (BMI ≥ 30 kg/m2), and extreme obesity (BMI ≥ 40 kg/m2). We built PRSscommon and PRSsrare using a range of methods (Clumping+Thresholding [C+T], PRS-CS, lassosum, gene-burden test). We selected the best-performing PRSs and assessed their performance in 36,757 European-ancestry unrelated participants with whole genome sequencing (WGS) data from the Trans-Omics for Precision Medicine (TOPMed) program. The best-performing PRScommon explained 10.1% of variation in BMI, and 18.3% and 22.5% of the susceptibility to obesity and extreme obesity, respectively, whereas the best-performing PRSrare explained 1.49%, and 2.97% and 3.68%, respectively. The PRSrare was associated with an increased risk of obesity and extreme obesity (ORobesity = 1.37 per SDPRS, Pobesity = 1.7x10-85; ORextremeobesity = 1.55 per SDPRS, Pextremeobesity = 3.8x10-40), which was attenuated, after adjusting for PRScommon (ORobesity = 1.08 per SDPRS, Pobesity = 9.8x10-6; ORextremeobesity= 1.09 per SDPRS, Pextremeobesity = 0.02). When PRSrare and PRScommon are combined, the increase in explained variance attributed to PRSrare was small (incremental Nagelkerke R2 = 0.24% for obesity and 0.51% for extreme obesity). Consistently, combining PRSrare to PRScommon provided little improvement to the prediction of obesity (PRSrare AUC = 0.591; PRScommon AUC = 0.708; PRScombined AUC = 0.710). In summary, while rare variants show convincing association with BMI, obesity and extreme obesity, the PRSrare provides limited improvement over PRScommon in the prediction of obesity risk, based on these large populations

Fast-Timing measurements in 100zr using labr3(ce) detectors coupled with gammasphere

In order to investigate the evolution of nuclear deformation in the region of the chart of nuclides around mass numbers A ' 110 and A ' 150, an experiment was performed at the Argonne National Laboratory where the gamma-decay radiation emitted from the fission fragments of 252Cf was measured using 51 Gammasphere detectors coupled with 25 LaBr3(Ce) detectors. In this work, a short description of the experimental setup is presented together with some preliminary results from the fast-Timing analysis of the 4+ state of the nucleus 100Zr. A lifetime value of τ = 50(28) ps was obtained using the Generalized Centroid Shift Method. This result agrees with the literature value of τ = 53(4) ps within one standard deviation