Background Immune checkpoint inhibitors have been widely implemented in current clinical practice. Although cancer occurs in ∼1 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.

Breast cancer is the most common malignancy diagnosed during pregnancy. Strong data on the genomic profile of pregnancy-associated breast cancer are lacking. This systematic review aims to integrate and analyze all existing data from the literature regarding the genomic background and the gene mutational patterns of pregnancy-associated breast cancer. Using various genomic analysis methods, multiple differentially expressed genes and numerous non-silent mutations have been detected. More particularly, our review demonstrates the aberrant expression of several oncogenes (e.g., MYC, SRC, FOS), tumor suppressor genes (e.g., TP53, PTEN, CAV1), apoptosis regulators (e.g., PDCD4, BCL2, BIRC5), transcription regulators (e.g., JUN, KLF1, SP110), genes involved in DNA repair mechanisms (e.g., Sig20, BRCA1, BRCA2, FEN1), in cell proliferation (e.g., AURKA, MKI67), in the immune response (e.g., PD1, PDL1), and in other significant biological processes (e.g., protein modification, internal cell motility). Further research on the genomic profile of pregnancy-associated breast cancer is urgently required in order to identify potential biomarkers facilitating early-stage diagnosis and individualized therapy.

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have emerged as novel treatment options in the management of advanced or metastatic breast cancer. MicroRNAs are endogenous non-coding 19–22-nucleotide-long RNAs that regulate gene expression in development and tumorigenesis. Herein, we systematically review all microRNAs associated with response to CDK4/6 inhibitors in solid tumors and hematological malignancies. Eligible articles were identified by a search of the MEDLINE and ClinicalTrials.gov databases for the period up to1 January 2021; the algorithm consisted of a predefined combination of the words “microRNAs”, “cancer” and “CDK 4/6 inhibitors”. Overall, 15 studies were retrieved. Six microRNAs (miR-126, miR-326, miR3613-3p, miR-29b-3p, miR-497 and miR-17-92) were associated with sensitivity to CDK4/6 inhibitors. Conversely, six microRNAs (miR-193b, miR-432-5p, miR-200a, miR-223, Let-7a and miR-21) conferred resistance to treatment with CDK4/6 inhibitors. An additional number of microRNAs (miR-124a, miR9, miR200b and miR-106b) were shown to mediate cellular response to CDK4/6 inhibitors without affecting sensitivity to treatment. Collectively, our review provides evidence that microRNAs could serve as predictive biomarkers for treatment with CDK4/6 inhibitors. Moreover, microRNA-targeted therapy could potentially maximize sensitivity to CDK4/6 inhibition.

Pregnancy-related cancer management represents a real challenge for both the patients and the physicians. The long-term neurodevelopmental outcome of children in utero exposed to chemotherapeutic agents has only recently been addressed. This review aims to systematically integrate and highlight all existing data from the literature regarding the effect of prenatal exposure to chemotherapy on fetal brain growth and child development. All eligible studies are based on validated neurodevelopmental testing scales (e.g., Bayley Scales of Infant Development, Wechsler Preschool and Primary Scale of Intelligence) and/or well-defined questionnaires. Our systematic review including 17 studies demonstrates that no major consequences on the neurodevelopment of children after in utero exposure to anti-cancer drugs have been reported; nevertheless, longer and more thorough follow-up with large-scale multicenter prospective studies is certainly required in order to draw firm conclusions.

Background: Pregnancy-associated breast cancer (PABC) defined as breast cancer diagnosed during gestation, lactation or within 1 year after delivery, represents a truly challenging situation with significantly increasing incidence rate. The genomic background of PABC has only recently been addressed while the underlying mechanisms of the disease still remain unknown. This analysis aims to further elucidate the frequency of PABC cases attributable to genetic predisposition and identify specific cancer susceptibility genes characterizing PABC. Methods: A comprehensive 94-cancer gene panel was implemented in a cohort of 20 PABC patients treated in our clinic and descriptive correlation was performed among the results and the patients’ clinicopathological data. Results: In the present study, 35% of PABC patients tested carried pathogenic mutations in two known cancer predisposition genes (BRCA1 and CHEK2). In total, 30% of the patients carried BRCA1 pathogenic variants. An additional 5% carried pathogenic variants in the CHEK2 gene. Variants of unknown/uncertain significance (VUS) in breast cancer susceptibility genes BRCA2, CHEK2 and BRIP1 were also identified in three different PABC patients (15%). Not all patients carrying germline mutations reported known family history of cancer. Conclusions: Genetic testing should be considered as an option for PABC patients since the disease is highly associated with genetic susceptibility among other predisposing factors. Germline mutation identification may further modify PABC management approach and improve the prognostic outcome.