Predictive gene expression profile for adjuvant taxane benefit in breast cancer in the MATADOR trial

The primary objective of the prospective, randomized, multicenter, phase 3 biomarker Microarray Analysis in breast cancer to Taylor Adjuvant Drugs Or Regimens trial (MATADOR: ISRCTN61893718) is to generate a gene expression profile that can predict benefit from either docetaxel, doxorubicin, and cyclophosphamide (TAC) or dose-dense scheduled doxorubicin and cyclophosphamide (ddAC). Patients with a pT1-3, pN0-3 tumor were randomized 1:1 between ddAC and TAC. The primary endpoint was a gene profile-treatment interaction for recurrence-free survival (RFS). We observed 117 RFS events in 664 patients with a median follow-up of 7 years. Hallmark gene set analyses showed significant association between enrichment in immune-related gene expression and favorable outcome after TAC in hormone receptor-negative, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) (triple-negative breast cancer [TNBC]). We validated this association in TNBC patients treated with TAC on H&amp;E slides; stromal tumor-infiltrating lymphocytes (sTILs) ≥20% was associated with longer RFS (hazard ratio 0.18, p = 0.01), while in patients treated with ddAC no difference in RFS was seen (hazard ratio 0.92, p = 0.86, pinteraction = 0.02).</p

High Involvement Management, High Performance Work Systems and Well-being

Studies on the impact of high-performance work systems on employees' well-being are emerging but the underlying theory remains weak. This paper attempts to develop theory of the effects on well-being of four dimensions of high-performance work systems: enriched jobs, high involvement management, employee voice, and motivational supports. Hypothesized associations are tested using multilevel models and data from Britain's Workplace Employment Relations Survey of 2004 (WERS2004). Results show that enriched jobs are positively associated with both measures of well-being: job satisfaction and anxiety–contentment. Voice is positively associated with job satisfaction, and motivational supports with neither measure. The results for high involvement management are not as predicted because it increases anxiety and is independent of job satisfaction