First-Line Chemotherapy for HER-2–Negative Metastatic Breast Cancer Patients Who Received Anthracyclines as Adjuvant Treatment

Learning Objectives After completing this course, the reader will be able to: Discuss the value of retreatment with anthracyclines for HER-2–negative metastatic breast cancer patients who received anthracyclines as adjuvant treatment.Discuss the role of liposomal anthracyclines, taxanes, and combinations without anthracyclines and taxanes, or innovative treatments, including target-based agents.Comment on the weakness and quality of available evidence. Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.co

A Two Micron All-Sky Survey View of the Sagittarius Dwarf Galaxy: VI. s-Process and Titanium Abundance Variations Along the Sagittarius Stream

We present high-resolution spectroscopic measurements of the abundances of titanium (Ti), yttrium (Y) and lanthanum (La) for M giant candidates of the Sagittarius (Sgr) dwarf spheroidal (dSph) + tidal tail system pre-selected on the basis of position and radial velocity. The majority of these stars show peculiar abundance patterns compared to those of nominal Milky Way (MW) stars. The overall [Ti/Fe], [Y/Fe], [La/Fe] and [La/Y] patterns with [Fe/H] of the Sgr stream plus Sgr core do resemble those seen in the Large Magellanic Cloud (LMC) and other dSphs, only shifted [Fe/H] by ~+0.4 from the LMC and by ~+1 dex from the other dSphs; these relative shifts reflect the faster and/or more efficient chemical evolution of Sgr compared to the other satellites, and show that Sgr has had an enrichment history more like the LMC than the other dSphs. By tracking the evolution of the abundance patterns along the Sgr stream we can follow the time variation of the chemical make-up of dSph stars donated to the MW halo by Sgr. This evolution demonstrates that while the bulk of the stars currently in the Sgr dSph are quite unlike those of the MW halo, an increasing number of stars farther along the Sgr stream have abundances like MW halo stars, a trend that shows clearly how the MW halo could have been contributed by present day satellite galaxies even if the present chemistry of those satellites is now different from typical halo field stars. Finally, we analyze the chemical abundances of a moving group of M giants among the Sgr leading arm stars at the North Galactic Cap, but having radial velocities unlike the infalling Sgr leading arm debris there. Through use of "chemical fingerprinting", we conclude that these northern hemisphere M giants also are Sgr stars, likely trailing arm debris overlapping the leading arm in the north.Comment: Accepted for publication in Ap

Functional Interaction Between BRCA1 and DNA Repair in Yeast May Uncover a Role of RAD50, RAD51, MRE11A, and MSH6 Somatic Variants in Cancer Development

In this study, we determined if BRCA1 partners involved in DNA double-strand break (DSB) and mismatch repair (MMR) may contribute to breast and ovarian cancer development. Taking advantage the functional conservation of DNA repair pathways between yeast and human, we expressed several BRCA1 missense variants in DNA repair yeast mutants to identify functional interaction between BRCA1 and DNA repair in BRCA1-induced genome instability. The pathogenic p.C61G, pA1708E, p.M775R, and p.I1766S, and the neutral pS1512I BRCA1 variants increased intra-chromosomal recombination in the DNA-repair proficient strain RSY6. In the mre11, rad50, rad51, and msh6 deletion strains, the BRCA1 variants p.C61G, pA1708E, p.M775R, p.I1766S, and pS1215I did not increase intra-chromosomal recombination suggesting that a functional DNA repair pathway is necessary for BRCA1 variants to determine genome instability. The pathogenic p.C61G and p.I1766S and the neutral p.N132K, p.Y179C, and p.N550H variants induced a significant increase of reversion in the msh2Δ strain; the neutral p.Y179C and the pathogenic p.I1766S variant induced gene reversion also, in the msh6Δ strain. These results imply a functional interaction between MMR and BRCA1 in modulating genome instability. We also performed a somatic mutational screening of MSH6, RAD50, MRE11A, and RAD51 genes in tumor samples from 34 patients and identified eight pathogenic or predicted pathogenic rare missense variants: four in MSH6, one in RAD50, one in MRE11A, and two in RAD51. Although we found no correlation between BRCA1 status and these somatic DNA repair variants, this study suggests that somatic missense variants in DNA repair genes may contribute to breast and ovarian tumor development

VizieR Online Data Catalog: Gamma Vel cluster membership and IMF (Prisinzano+, 2016)

We derived a list as complete as possible of confirmed members of the young open cluster Gamma Velorum, with the aim of deriving general cluster properties such as the IMF. We used all available spectroscopic membership indicators within the Gaia-ESO public archive, based on spectra acquired with FLAMES a the VLT using the GIRAFFE intermediate-resolution spectrograph. In addition, we used literature photometry and X-ray data. For each membership criterion, we derived the most complete list of candidate cluster members. Then, we considered photometry, gravity, and radial velocities as necessary conditions for selecting a subsample of candidates whose membership was confirmed by using the lithium and Halpha lines and X-rays as youth indicators. Table 5 lists the fundamental parameters of the confirmed and possible members in Gamma Velorum, i.e. photometry, radial velocities, equivalent widths of the lithium line, the Halpha activity index, the X-ray flag, the gravity gamma index and the stellar masses. Finally the binarity and membership flags are given. (1 data file)

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

Dynamics of SARS-CoV-2-Specific B Cell Memory Responses in Infected and Vaccinated Individuals

Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly resulted in a pandemic constituting a global health emergency. As an indicator of long-term immune protection from reinfection with the SARS-CoV-2 virus, the presence of memory B cells (MBCs) should be evaluated. Since the beginning of COVID-19 pandemic, several variants of concerns have been detected, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1/B.1.1.28.1), Delta (B.1.617.2), and Omicron (BA.1) variants with several different mutations, causing serious concern regarding the increased frequency of reinfection, and limiting the effectiveness of the vaccine response. At this regard, we investigated SARS-CoV-2-specific cellular immune responses in four different cohorts: COVID-19, COVID-19 infected and vaccinated, vaccinated, and negative subjects. We found that MBC response to SARS-CoV-2 at more than 11 months postinfection was higher in the peripheral blood of all COVID-19 infected and vaccinated subjects respect to all the other groups. Moreover, to better characterize the differences of SARS-CoV-2 variants immune responses, we genotyped SARS-CoV-2-positive samples from the patients' cohort. We found a higher level of immunoglobulin M+ (IgM+) and IgG+ spike MBCs in SARS-CoV-2-positive patients (5-8 months after symptoms onset) infected with the SARS-CoV-2-Delta variant compared with the SARS-CoV-2-Omicron variant implying a higher immune memory response. Our findings showed that MBCs persist more than 11 months after primary infection indicating a different involvement of the immune system according to the different SARS-CoV-2 variant that infected the host