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Question: Medical education is perceived as stressful. The purpose of this study was to explore the possible effect of academic examination stress on cortical long-term potentiation (LTP)-like plasticity in a group of university students. Methods: The study included nine healthy medical students (males: mean age 30.2±4.3 SE) and was conducted during a major exam period (stressed) and 5weeks later after the exams (non-stressed). Facilitatory associative plasticity was induced by paired associative stimulation (PAS) in the human motor cortex (PAS-25 protocol). In addition, students were required to fill the Perceived Stress Scale 10 (PSS) questionnaire. Results: Sixty minutes after PAS-25 induction protocol, students showed lower amounts of potentiation during the exam period compared with after the exams (p =0.039). The average PSS score significantly higher during the “stressed” period (P =0.024). LTP-like plasticity showed an inverse correlation with the perceived stress. Conclusions: Academic stress appears to affect LTP-like plasticity in students. Deficit in attention and impairment of N-methyl-d-aspartate receptor-dependent neural plasticity associated with stress might underlie our findings. Larger scale studies are needed to address the interrelationship between LTP-like plasticity and academic performance. [ABSTRACT FROM AUTHOR]

Cisplatin and paclitaxel are active in triple-negative breast cancer (TNBC). Despite different mechanisms of action, effective predictive biomarkers to preferentially inform drug selection have not been identified. The homologous recombination deficiency (HRD) assay (Myriad Genetics, Inc.) detects impaired double-strand DNA break repair and may identify patients with BRCA1/2-proficient tumors that are sensitive to DNA-targeting therapy. The primary objective of TBCRC 030 was to detect an association of HRD with pathologic response [residual cancer burden (RCB)-0/1] to single-agent cisplatin or paclitaxel. This prospective phase II study enrolled patients with germline BRCA1/2 wild-type/unknown stage I–III TNBC in a 12-week randomized study of preoperative cisplatin or paclitaxel. The HRD assay was carried out on baseline tissue; positive HRD was defined as a score ≥33. Crossover to an alternative chemotherapy was offered if there was inadequate response. One hundred and thirty-nine patients were evaluable for response, including 88 (63.3%) who had surgery at 12 weeks and 51 (36.7%) who crossed over to an alternative provider-selected preoperative chemotherapy regimen due to inadequate clinical response. HRD results were available for 104 tumors (74.8%) and 74 (71.1%) were HRD positive. The RCB-0/1 rate was 26.4% with cisplatin and 22.3% with paclitaxel. No significant association was observed between HRD score and RCB response to either cisplatin [odds ratio (OR) for RCB-0/1 if HRD positive 2.22 (95% CI: 0.39–23.68)] or paclitaxel [OR for RCB-0/1 if HRD positive 0.90 (95% CI: 0.19–4.95)]. There was no evidence of an interaction between HRD and pathologic response to chemotherapy. In this prospective preoperative trial in TNBC, HRD was not predictive of pathologic response. Tumors were similarly responsive to preoperative paclitaxel or cisplatin chemotherapy. • This trial prospectively evaluated the predictive capacity of the HRD biomarker for pathologic response in early TNBC. • Pathologic responses to preoperative cisplatin or taxane monotherapy in germline BRCA1/2 wild-type TNBC were similar. • HRD score was not predictive of pathologic response to either cisplatin or paclitaxel chemotherapy. • HRD testing cannot be recommended as a tool to select chemotherapy agents in the management of early-stage TNBC. [ABSTRACT FROM AUTHOR]

The ALTERNATIVE trial randomized 355 patients (pts) with HER2+/HR+ metastatic BC to receive as 1st-line therapy lapatinib (L) + trastuzumab (T) + aromatase inhibitors (AI) or T + AI or L + AI. The neoadjuvant PAMELA trial tested a chemo-free regimen of L + T on HER2+ pts, combined with letrozole or tamoxifen in HR+ tumors. We explored the hypothesis that gene expression may help predicting benefit from anti-HER2 therapy in combination with ET. The expression of 55 BC-related genes was evaluated from FFPE tumors using the nCounter. The PAM50 subtype distribution and the association of the expression of each gene (continuous variable) with progression-free survival (PFS) was evaluated using univariate Cox-models. Median PFS was calculated using the Kaplan-Meier method. Clinical benefit (CB) was defined as complete or partial response or stable disease at 6 months. The Cutoff Finder tool was used to find an optimal gene expression cut-off with CB as the endpoint. Logistic regression was used to evaluate the association of gene expression with pathologic complete resonse (pCR) and CB. In ALTERNATIVE, 60 tumors (16.9%) were analyzed: 57% HER2-enriched, 20% Luminal B, 12% Luminal A, 8% Normal-like and 3% Basal-like. Median PFS in ERBB2-high group (above the median) was higher compared to ERBB2-low group (11.0 vs 5.6 months; Hazard Ratio [HazR]=0.49; p = 0.006). ERBB2 was found more expressed in pts with CB. CB rate was higher in the ERBB2-high group compared to ERBB2-low group (54% vs 22%; p = 0.013). An optimal ERBB2 mRNA cutoff (2.923) for predicting CB (AUC=0.68; odds ratio [OR]=1.49, p = 0.014; PFS HazR=0.46, p = 0.022) was then identified. The same ERBB2 cutoff in PAMELA baseline tumor samples (n = 77) was found significantly associated with pCR (43.8% in ERBB2-high vs. 11.5% in ERBB2-low; adjusted OR = 4.45; p = 0.041). ERBB2 mRNA expression is a robust predictor of response and survival outcome in HER2+/HR+ BC following HER2-blockade and ET. Our study identifies a common biomarker between pCR improvement (OR ∼4.5) in early disease and CB in the advanced setting (PFS HazR of ∼0.50). Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). Has not received any funding. N. Chic: Travel / Accommodation / Expenses: Eisai. F. Schettini: Travel / Accommodation / Expenses: Celgene; Travel / Accommodation / Expenses: Pfizer. M. Vidal: Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony: Daiichi Sankyo. M. Muñoz: Travel / Accommodation / Expenses: Roche. J. Cortés: Honoraria (self): Novartis; Honoraria (self): Eisai; Honoraria (self): Roche; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Celgene; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Biothera Pharmaceutical; Advisory / Consultancy: Merus; Advisory / Consultancy: Seattle Genetics. A. Llombart-Cussac: Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche/Genentech. M. Rimawi: Advisory / Consultancy: GlaxoSmithKline; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: MacroGenics; Advisory / Consultancy: Novartis; Advisory / Consultancy: Daiichi Sankyo. A. Prat: Advisory / Consultancy: Nanostring Techonologies. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]