Introduction: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with an increased risk of recurrence and cancer-related death. Unlike hormone receptor-positive or HER2-positive breast cancers, there are limited targeted therapies available to treat TNBC and cytotoxic chemotherapy remains the mainstay of treatment. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate targeting Trop-2 expressing cells and selectively delivering SN-38, an active metabolite of irinotecan.
Areas covered: This review covers the mechanism of action, safety and efficacy of sacituzumab govitecan in patients with previously treated, metastatic TNBC. Additionally, efficacy data in other epithelial malignancies is included based on a PubMed search for ‘sacituzumab govitecan’ and ‘clinical trial’.
Expert opinion: Sacituzumab govitecan has promising anti-cancer activity in patients with metastatic TNBC previously treated with at least two prior lines of systemic therapy based on a single arm Phase I/II clinical trial. A confirmatory Phase III randomized clinical trial is ongoing. Sacituzumab govitecan has a manageable side effect profile, with the most common adverse events being nausea, neutropenia, and diarrhea. The activity of sacituzumab govitecan likely extends beyond TNBC with promising early efficacy data in many other epithelial cancers, including hormone receptor-positive breast cancer. 相似文献
This meta-analysis focuses on the accuracy of upgrading to clinically significant prostate cancer (PCa) by multiparametric magnetic resonance imaging-targeted biopsy (MRI-TB) versus systematic biopsy (SB). We searched the Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, and Literatura Latino Americana em Ciências da Saúde databases through January 2020 for comparative, retrospective/prospective, paired-cohort, and randomized clinical trials with paired comparisons. The population consisted of patients with low-risk PCa in active surveillance with at least 1 index lesion on imaging. We evaluated the quality of evidence by using the Quality Assessment of Diagnostic Accuracy Studies-2 score. Group comparisons considered the differences between the area under the curve summary receiver operating characteristic curve in a 2-tailed method. We also compared the positive predictive value of the best single method (MRI-TB or SB) and the referral study test (combined biopsy, a combination of MRI-TB and SB). The meta-analysis included 6 studies enrolling 741 patients. The pooled sensitivity for the 2 groups was 0.79 (95% confidence interval, 0.74-0.83; I2 = 75%) and 0.67 (95% confidence interval, 0.63-0.74; I2 = 55.4%), respectively. The area under the curve for the MRI-TB and SB groups were 0.99 and 0.92 (P < .001), respectively. The positive predictive value for the MRI-TB and combined biopsy groups were similar. The accumulated evidence suggests better results for MRI-TB compared with SB. Therefore, use of MRI-TB alone may be preferable in patients in active surveillance harboring low-risk PCa. 相似文献
The current study investigated the effects of two exercise interventions on cognitive function amongst breast cancer survivors.
Design
Pilot randomised-controlled trial.
Methods
Seventeen female cancer survivors (mean: 62.9 ± 7.8 years) were randomised into three groups: high-intensity interval training (HIIT, n = 6); moderate-intensity continuous training (MOD, n = 5); or wait-list control (CON, n = 6). The HIIT and MOD groups exercised on a cycle ergometer 3 days/week for 12-weeks. Primary outcomes were cognitive function assessments utilising CogState. Secondary outcomes were resting middle cerebral artery blood flow velocity, cerebrovascular reactivity and aerobic fitness (VO2peak). Data were analysed with General Linear Mixed Models and Cohen’s d effect sizes were calculated.
Results
All 17 participants who were randomised were available for follow-up analysis and adherence was similar for HIIT and MOD (78.7 ± 13.2% vs 79.4 ± 12.0%; p = 0.93). Although there were no significant differences in the cognitive and cerebrovascular outcomes, HIIT produced moderate to large positive effects in comparison to MOD and CON for outcomes including episodic memory, working memory, executive function, cerebral blood flow and cerebrovascular reactivity. HIIT significantly increased VO2peak by 19.3% (d = 1.28) and MOD had a non-significant 5.6% (d = 0.72) increase, compared to CON which had a 2.6% decrease.
Conclusions
This study provides preliminary evidence that HIIT may be an effective exercise intervention to improve cognitive performance, cerebrovascular function and aerobic fitness in breast cancer survivors. Considering the sample size is small, these results should be confirmed through larger clinical trials. 相似文献
Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes. 相似文献