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Background Several accomplishments have been achieved in triple-negative breast cancer (TNBC) research over the last year. The phase III IMpassion130 trial comparing chemotherapy plus atezolizumab versus chemotherapy plus placebo brought breast cancer into the immunotherapy era. Nevertheless, despite encouraging results being obtained in this trial, many open questions remain. Main body A positive overall survival outcome was achieved only in PD-L1 + TNBC patients, suggesting a need to enrich the patient population more likely to benefit from an immunotherapeutic approach. Moreover, it remains unknown whether single-agent immunotherapy might be a good option for some patients. In this context, the discovery and implementation of novel and appropriate biomarkers are required. Focusing on the early onset of TNBC, neoadjuvant trials could represent excellent in vivo platforms to test immunotherapy agents and their potential combinations, allowing the performance of translational studies for biomarker implementation and improved patient selection. Conclusion The aim of our review is to present recent advances in TNBC treatment and to discuss open issues in order to better define potential future directions for immunotherapy in TNBC.

corporate boards , audit committees , earnings management , accounting accruals ,

Triple-negative breast cancer (TNBC) is not a unique disease, encompassing multiple entities with marked histopathological, transcriptomic and genomic heterogeneity. Despite several efforts, transcriptomic and genomic classifications have remained merely theoretic and most of the patients are being treated with chemotherapy. Driver alterations in potentially targetable genes, including PIK3CA and AKT, have been identified across TNBC subtypes, prompting the implementation of biomarker-driven therapeutic approaches. However, biomarker-based treatments as well as immune checkpoint inhibitor-based immunotherapy have provided contrasting and limited results so far. Accordingly, a better characterization of the genomic and immune contexture underpinning TNBC, as well as the translation of the lessons learnt in the metastatic disease to the early setting would improve patients’ outcomes. The application of multi-omics technologies, biocomputational algorithms, assays for minimal residual disease monitoring and novel clinical trial designs are strongly warranted to pave the way toward personalized anticancer treatment for patients with TNBC.

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The harnessing in clinical practice of cyclin-dependent kinases 4/6 inhibitors, namely palbociclib, ribociclib, and abemaciclib, has substantially changed the therapeutic approach for hormone receptor-positive metastatic breast cancer (BC). Phase II–III clinical trials evaluating the addition of these agents to standard endocrine therapy reported consistent improvements in response rates and progression-free survival as well as manageable toxicity profiles and excellent impact on patients’ quality of life. Hence, pivotal trials provided comparable results among different cyclin-dependent kinases 4/6 inhibitors, there is an increasing interest in finding substantial differences in order to implement their use in clinical practice. The aim of this paper is to summarize the current evidences raised from preclinical and clinical studies on cyclin-dependent kinases 4/6 inhibitors in BC, focusing on differences in terms of pharmacological properties, toxicity profile, and patients’ quality of life.

SUMMARY Mandatory auditor rotation was recently proposed for the European Union and is also under consideration in the United States. There has been little research into either the benefits or costs of rotation in a true mandatory setting that could inform intelligent policy making. Our paper helps fill this gap by examining Italy, where mandatory rotation of auditors has been required since 1975. We find that outgoing auditors do not shirk on effort (or quality), but final-year fees are 7 percent higher than normal, which may indicate opportunistic pricing. The fees of incoming auditors are discounted by 16 percent even though they have abnormally higher engagement hours in the first year (17 percent), which is suggestive of lowballing. However, subsequent fees are abnormally higher and exceed the initial fee discount. Thus, the costs of mandatory rotation are nontrivial. Higher costs could be acceptable if rotation improves audit quality, but we find evidence of the opposite. Namely, the quality of audited earnings is lower in the first three years following rotation, relative to later years of auditor tenure. Since rotation is costly and earnings quality improves with longer auditor tenure, the evidence from Italy does not support the case for mandatory rotation.

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