Genomic features of rapid versus late relapse in triple negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogeneous disease and we have previously shown that rapid relapse of TNBC is associated with distinct sociodemographic features. We hypothesized that rapid versus late relapse in TNBC is also defined by distinct clinical and genomic features of primary tumors. METHODS: Using three publicly-available datasets, we identified 453 patients diagnosed with primary TNBC with adequate follow-up to be characterized as 'rapid relapse' (rrTNBC; distant relapse or death ≤2 years of diagnosis), 'late relapse' (lrTNBC; > 2 years) or 'no relapse' (nrTNBC: > 5 years no relapse/death). We explored basic clinical and primary tumor multi-omic data, including whole transcriptome (n = 453), and whole genome copy number and mutation data for 171 cancer-related genes (n = 317). Association of rapid relapse with clinical and genomic features were assessed using Pearson chi-squared tests, t-tests, ANOVA, and Fisher exact tests. We evaluated logistic regression models of clinical features with subtype versus two models that integrated significant genomic features. RESULTS: Relative to nrTNBC, both rrTNBC and lrTNBC had significantly lower immune signatures and immune signatures were highly correlated to anti-tumor CD8 T-cell, M1 macrophage, and gamma-delta T-cell CIBERSORT inferred immune subsets. Intriguingly, lrTNBCs were enriched for luminal signatures. There was no difference in tumor mutation burden or percent genome altered across groups. Logistic regression mModels that incorporate genomic features significantly outperformed standard clinical/subtype models in training (n = 63 patients), testing (n = 63) and independent validation (n = 34) cohorts, although performance of all models were overall modest. CONCLUSIONS: We identify clinical and genomic features associated with rapid relapse TNBC for further study of this aggressive TNBC subset.

Statewide implementation of an evidence-based trauma intervention in schools.

The goal of the current article is to describe the implementation and outcomes of an innovative statewide dissemination approach of the evidence-based trauma intervention Cognitive Behavioral Intervention for Trauma in Schools (CBITS). In the context of a 2-year statewide learning collaborative effort, 73 CBITS groups led by 20 clinicians from 5 different school-based mental health provider organizations served a total of 350 racially and ethnically diverse (66.9% Hispanic, 26.2% Black/African American, 43.7% White, and 30.1% Other), majority female (61%) children, averaging 12.2 years (SD = 2.4, range 8-19). Of the 350 children who began CBITS, 316 (90.3%) successfully completed treatment. Children demonstrated significant reductions in child posttraumatic stress disorder (PTSD) symptoms (42% reduction, d = .879) and problem severity (25% reduction, d = .396), and increases in child functioning, t(287) = -3.75, p < .001 (5% increase, d = .223). Findings point to the need, feasibility, and positive impact of implementing and scaling up school-based interventions for students suffering from posttraumatic stress. (PsycINFO Database Record

A method to optimize the response range while maintaining Rorschach Comprehensive System validity.

Brief and lengthy Rorschach records have been identified as common problems in protocol administration. Clinicians have debated how to prevent overly short and long records, but they have been reluctant to alter standardized administration for fear of introducing bias. The present study examines a nonintrusive method for constraining responses by prompting for an extra response when only one is offered per card and by removing the card after four responses are given. Among patients who typically produce brief records, consisting of a residential sample of civil and forensic patients with a range of disordered thinking, the alternative administration method demonstrated improved Comprehensive System validity in assessing thought disorder and eliminated the need to readminister the test due to fewer than 14 responses. The findings have clinical implications for protocol administration with thought-disordered populations that typically produce brief records.