SAUL, a single-arm study of atezolizumab for chemotherapy-pretreated locally advanced or metastatic carcinoma of the urinary tract: outcomes by key baseline factors, PD-L1 expression and prior platinum therapy

Background The impact of pretreatment factors on immune checkpoint inhibition in platinum-refractory advanced urothelial cancer (aUC) deserves further evaluation. The aim was to study the association of Bellmunt risk factors, time from last chemotherapy (TFLC), previous therapy and PD-L1 expression with atezolizumab efficacy in platinum-refractory aUC. Patients and methods This was a post-hoc analysis of patients who had received prior cisplatin or carboplatin in the prospective, single-arm, phase IIIb SAUL study (NCT02928406). Patients were treated with 3-weekly atezolizumab 1200 mg intravenously. The primary outcome was overall survival (OS). Relationships were analysed using Cox regression and long-rank test. Results Of 997 patients in SAUL, 969 were eligible for this analysis. The number of Bellmunt risk factors was associated with OS (P 6 months, 7.75 versus 11.6 months for PD-L1 expression on <1% of tumour-infiltrating immune cells (ICs) (IC0)/expression on 1% to <5% of tumour-infiltrating ICs (IC1) versus expression on ≥5% of tumour-infiltrating ICs (IC2/3) and 10.2 versus 7.8 months for prior versus no prior perioperative chemotherapy, respectively. The type of platinum compound and number of previous treatment lines were not associated with outcomes. Conclusions Post-platinum atezolizumab is active in aUC, irrespective of previous platinum compound and lines of therapy. Bellmunt risk stratification, PD-L1 expression, TFLC and perioperative chemotherapy were identified as prognostic factors for OS with second-line atezolizumab, indicating the need for novel prognostic signatures for immunotherapy-treated patients with aUC

Prognostic role of microRNAs in breast cancer: A systematic review

MicroRNAs (miRNAs) have been found to play an important role in breast cancer, functioning either as potential oncogenes or tumor suppressor genes, but their role in the prognosis of patients remains unclear. The aim of the present review study is to highlight recent preclinical and clinical studies performed on both circulating and tissue-specific miRNAs and their potential role as prognostic markers in breast cancer. We systematically searched the PubMed database to explore the prognostic value of miRNAs in breast cancer. After performing the literature search and review, 117 eligible studies were identified. We found that 110 aberrantly expressed miRNAs have been associated with prognosis in breast cancer. In conclusion, the collective data presented in this review indicate that miRNAs could serve as novel prognostic tools in breast cancer, while the clinical application of these findings has yet to be verified. Copyright: © Zografos et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0)

Immunotherapy in HER2-Positive Breast Cancer: A Systematic Review

Introduction: 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. Methods: 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. Results: Twelve clinical trials and 2 case reports were identified in our study. Conclusion: The reported clinical trials highlight that checkpoint inhibition seems to be promising in metastatic, neoadjuvant, and adjuvant settings of HER2-positive breast cancer. © 2021 S. Karger AG, Basel. Copyright: All rights reserved

Discrepancies of current recommendations in breast cancer follow-up: a systematic review

Introduction: Management and optimal follow-up of early breast cancer survivors remain up to this day a challenge due to the lack of well-established guidelines. Multiple medical societies, organizations and working groups have provided recommendations for follow-up but there is no uniform, globally approved algorithm to guide clinical practice. Methods: A systematic review was performed to identify and evaluate discrepancies between available guidelines for the follow-up of breast cancer survivors. Results: Differences in the follow-up schedule, laboratory and imaging investigations were noted. In the clinical practice setting, the situation is complicated further by clinicians who often request unnecessary tests not currently incorporated in any of the existing guidelines. Conclusions: Follow-up of patients with early breast cancer needs to become standardized and prospective clinical trials focusing on optimal follow-up are more than mandatory. © 2019, The Japanese Breast Cancer Society

Hypomethylation of retrotransposable elements correlates with genomic instability in non-small cell lung cancer

LINE-1 and Alu elements are non-LTR retrotransposons, constituting together over 30% of the human genome and they are frequently hypomethylated in human tumors. A relationship between global hypomethylation and genomic instability has been shown, however, there is little evidence to suggest active role for hypome-thylation-mediated reactivation of retroelements in human cancer. In our study, we examined by Pyrosequencing the methylation levels of LINE-1 and Alu sequences in 48 primary nonsmall cell carcinomas and their paired adjacent tissues. We demonstrate a significant reduction of the methylation levels of both elements (p = 7.7 × 10-14 and 9.6 × 10-7, respectively). The methylation indices of the 2 elements correlated (p = 0.006), suggesting a possible common mechanism for their methylation maintenance. Genomic instability was measured utilizing 11 fluorescent microsatellite markers located on lung cancer hot-spot regions such as 3p, 5q 9p, 13q and 17p. Hypomethylation of both transposable elements was ass o5ciated with increased genomic instability (LINE, p = 7.1 × 10-5; Alu, p = 0.008). The reduction of the methylation index of LINE-1 and Alu following treatment of 3 lung cell lines with 5-aza-2&apos;-deoxycitidine, consistently resulted in increased expression of both elements. Our study demonstrates the strong link between hypomethylation of transposable elements with genomic instability in non-small cell lung cancer and provides early evidence for a potential active role of these elements in lung neoplasia. As demethylating agents are now entering lung cancer trials, it is imperative to gain a greater insight into the potential reactivation of silent retrotransposons in order to advance for the clinical utilization of epigenetics in cancer therapy. © 2008 Wiley-Liss, Inc

Taxanes during pregnancy in cervical cancer: A systematic review and pooled analysis

Background: Cervical cancer is one of the most common malignancies diagnosed during pregnancy. Taxanes administration has been established as theurapetic regimen in non pregrant women. Objectives: This systemic review and meta-analysis aims to synthesize all available data from cervical cancer series in pregnant women and evaluate the efficacy and safety of taxanes during pregnancy. Search strategy: Eligible articles were identified by a search of ClinicalTrial.gov and MEDLINE databases for the period 01/01/2000 up to 31/11/2017; The algorithm consisted of a predefined combination of the words “cervical”, “cancer”, “taxanes” and “pregnancy”. Selection criteria: PRISMA guidelines were applied in this study. The literature search and data extraction from all studies that examined the efficacy and safety of taxanes in pregnancy, were done by two independent investigators. Quantitative synthesis of the published articles was performed. Data collection and analysis: Overall eight articles were retrieved. In all cases (14 pregnancies, 14 newborns) the use of taxanes in combination with platinum derivatives resulted in the birth of alive neonates, with not any miscarriage. The taxane derivative used in all cases was paclitaxel, combined with Cisplatin (13 pregnancies) and Carboplatin (one pregnancy). Results: Complete and partial response was achieved in 7.2% and 92.9% of cervical cancer patients. In the majority of cases chemotherapy was well tolerated. The median progression-free survival was 48.5 months. Conclusion: Taxanes administration during the 2nd and 3rd trimester of pregnancy is a safe choice. © 2019 Elsevier Lt