No abstract

Background: Immune checkpoint inhibitors have been widely implemented in current clinical practice. Although cancer occurs in w1 out of 1000 pregnancies, treatment remains challenging. Until now, limited data exist regarding immunotherapy administration during pregnancy. This systemic review aims to synthesize all available data from immunotherapy administration in pregnant women and evaluate the efficacy and safety of immunotherapy during pregnancy. Patients and methods: Eligible studies were identified by a search of the PubMed Medline database and Food and Drug Administration Adverse Events Reporting System Public Dashboard for the period 1 January 2000 to 1 April 2021; the algorithm consisted of a predefined combination of the words 'immunotherapy', 'cancer' and 'pregnancy'. PRISMA guidelines were applied in this study. Results: Overall, seven articles (seven pregnancies, nine neonates) were retrieved. The mean duration of immunotherapy administration was 9.8 weeks [standard deviation (SD): 11.27; median: 7.0; range: 1-32]. In all cases specified, melanoma was the malignancy reported. The mean gestational age at delivery was 30.4 weeks (SD: 5.03; median: 32.0; range: 24-38), whereas the mean weight of neonates at delivery was 1267 g (SD: 412.0; median: 1400; range: 590-1701). Only one neonate was born term at 38 weeks of pregnancy (11.1%; 1/9). Complications during pregnancy were observed in 71.4% of cases: intrauterine growth restriction (three cases), HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count) (one case), placental insufficiency (one case) and low fetal heart rate (one case). The mean progression-free survival and overall survival were 16.0 and 25.2 months, respectively. Conclusion:The administration of immune checkpoint inhibitors during pregnancy is associated with increased incidence of pregnancy complications, prematurity and low birth weight. The administration of these regimens is not recommended during gestation. Whenever applied, close monitoring of the mother and the fetus is required.

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.

Background Over than one third (28–58%) of pregnancy-associated breast cancer (PABC) cases are characterized by positive epidermal growth factor receptor 2-positive (HER2) expression. Trastuzumab anti-HER2 monoclonal antibody is still the benchmark treatment of HER2-positive breast tumors. However, FDA has categorized Trastuzumab as a category D drug for pregnant patients with breast cancer. This systemic review aims to synthesize all currently available data of trastuzumab administration during pregnancy and provide an updated view of the effect of trastuzumab on fetal and maternal outcome. Methods Eligible articles were identified by a search of MEDLINE bibliographic database and ClinicalTrials.gov for the period up to 01/09/2020; The algorithm consisted of a predefined combination of the words “breast”, “cancer”, “trastuzumab” and “pregnancy”. This study was performed in accordance with the PRISMA guidelines. Results A total of 28 eligible studies were identified (30 patients, 32 fetuses). In more than half of cases, trastuzumab was administered in the metastatic setting. The mean duration of trastuzumab administration during gestation was 15.7 weeks (SD: 10.8; median: 17.5; range: 1–32). Oligohydramnios or anhydramnios was the most common (58.1%) adverse event reported in all cases. There was a statistically significant decrease in oligohydramnios/anhydramnios incidence in patients receiving trastuzumab only during the first trimester (P = 0.026, Fisher’s exact test). In 43.3% of cases a completely healthy neonate was born. 41.7% of fetuses exposed to trastuzumab during the second and/or third trimester were born completely healthy versus 75.0% of fetuses exposed exclusively in the first trimester. All mothers were alive at a median follow-up of 47.0 months (ranging between 9 and 100 months). Of note, there were three cases (10%) of cardiotoxicity and decreased ejection fraction during pregnancy. Conclusions Overall, treatment with trastuzumab should be postponed until after delivery, otherwise pregnancy should be closely monitored.