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Breast carcinoma is the most frequent and the second leading cause of cancer mortality in women worldwide. Current treatment decisions are based on tumor profiling of the initial tissue biopsy.Cancer though evolves both spatially and temporarily in a significant percentage of patients during treatment. However, sequential biopsies from the primary tumor or its metastatic sites are not either convenient or feasible in the majority of cases. In the era of precision medicine, analysis of circulating bloodbased biomarkers in the field of liquid biopsies provides an insight into the dynamic molecular profiling of the primary tumor and its metastases, in a relatively non-invasive way. The latter permits not only patient stratification but also longitudinal evaluation of treatment response, when incorporated into clinical trials. This review summarizes the results from recent and ongoing circulating tumor DNA (ctDNA)based biomarker-driven clinical trials, with respect to ctDNA analysis' predictive role, both in adjuvant, neo-adjuvant, and metastatic setting. Furthermore, current challenges in ctDNA analysis applications are critically discussed, including pre-analytical and analytical issues, and future perspectives in this field, through the conduct of well-designed, multicenter, randomized, large-scale, biomarker-stratified trials, with robust statistical methods. Despite in its infancy, ctDNA analysis holds great promise as a minimally invasive tool regarding tailored, personalized treatment guidance for breast cancer patients.

Recently, immunotherapy has shown promising results in solid tumors. To the best of our knowledge, this is the first systematic review of published literature synthesizing all the available data and evaluating both the efficacy and safety of pembrolizumab in endometrial cancer. The present study was performed in accordance with the PRISMA guidelines. Eligible articles were identified by searching the MEDLINE and ClinicalTrials.gov databases, using a predefined combination of the terms 'endometrial cancer' and 'pembrolizumab'. Overall, nine articles incorporating data from 712 patients were eligible. Pembrolizumab was demonstrated to be an effective and safe therapeutic option for the management of advanced/metastatic endometrial cancer. Results of ongoing trials evaluating either pembrolizumab alone or in combination with other antineoplastic regimens are expected to confirm its efficacy in this setting of patients. Pembrolizumab appears to be both durable and robust in endometrial cancer. However, there is an emerging need for novel predictive biomarkers to guide clinical practice. Contents 1. Introduction 2. Sources and study selection 3. Data on efficacy and safety 4. Discussion 5. Conclusion

<b><i>Introduction:</i></b> The clinical outcome of HER2-positive breast cancer patients changed with the use of anti-Her therapies, though it still remains an aggressive and fatal disease. Implementation of immune checkpoint inhibitors in HER2-positive Breast cancer is a concept supported by the reported biological and preclinical data. <b><i>Methods:</i></b> We conducted a systematic review of the current literature involving immune checkpoint inhibitors alone or in combination with targeted therapies or chemotherapy finalized or running in HER2-positive breast cancer. <b><i>Results:</i></b> Twelve clinical trials and 2 case reports were identified in our study. <b><i>Conclusion:</i></b> The reported clinical trials highlight that checkpoint inhibition seems to be promising in metastatic, neoadjuvant, and adjuvant settings of HER2-positive breast cancer.

AimThe aim of this study was to investigate the association of endocrine complications after ICI immunotherapy with progression-free survival (PFS) and overall survival (OS) in a large single-center oncological cohort.Patients and MethodsIn total, 351 patients were included in the analysis, 248 men (70.7%) and 103 women (29.3%). The median age was 66 years. Patients had a variety of cancer types, namely, bladder cancer (131, 37.3%), renal cancer (89, 25.4%), lung cancer (74, 21.1%), ovarian cancer (22, 6.3%), and other types of cancer (35, 10%). The majority (314, 89.4%) were classified as stage IV, while 10.6% (37) were classified as stage III. Most of the patients received immunotherapy with anti-PD1 agents (262, 74.6%) and the rest with anti-PD-L1 agents (89, 25.4%). Kaplan–Meier estimates were used to describe and visualize the effect of categorical variables on OS and PFS. Survival analysis was performed by Kaplan–Meier curves, and survival differences between groups were estimated using the log-rank test. The estimation of the prognostic value of several variables with patients’ survival was made by Cox regression models.ResultsIn total, 68 (19.4%) of patients presented an endocrine complication after immunotherapy with ICIs. Specifically, 66 (18.8%) had thyroid dysfunction, 1 patient presented hypophysitis (0.3%), and 1 patient had a combination of thyroid dysfunction and hypophysitis (0.3%). Patients with an endocrine complication had mPFS of 15 months (95% CI 11.0–18.9 months), while in those without endocrine complication mPFS was 7 months (95% CI 6.1–7.9 months, p &lt; 0.001). Similarly, median OS (mOS) was statistically significant lower in the patients’ group without endocrine complication. In fact, mOS was 51 months (95% CI 39.3–62.7 months) for these patients. The presence of endocrine complications after immunotherapy with ICIs retained its significance in terms of longer PFS (HR 0.57, 95% CI 0.39–0.81) and OS (HR 0.53, 95% CI 0.32–0.90) after multivariate analysis.ConclusionsICI endocrinopathies may be a positive predictor of immunotherapy response.

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