To provide a breast cancer (BC) methylotype classification by genome-wide CpG islands bisulfite DNA sequencing. Materials & methods: XmaI-reduced representation bisulfite sequencing DNA methylation sequencing method was used to profile DNA methylation of 110 BC samples and 6 normal breast samples. Intrinsic DNA methylation BC subtypes were elicited by unsupervised hierarchical cluster analysis, and cluster-specific differentially methylated genes were identified. Results & conclusion: Overall, six distinct BC methylotypes were identified. BC cell lines constitute a separate group extremely highly methylated at the CpG islands. In turn, primary BC samples segregate into two major subtypes, highly and moderately methylated. Highly and moderately methylated superclusters, each incorporate three distinct epigenomic BC clusters with specific features, suggesting novel perspectives for personalized therapy.

Epstein-Barr virus-associated gastric cancer [EBV-associated GC, EBV( +) GC] is a distinct molecular subtype of gastrointestinal (GI) cancers. It accounts for up to 10% of all molecular subtypes of gastric cancer (GC). It has unique genetic and epigenetic features, which determine its definitive phenotype with male and younger age predominance, proximal stomach localization, and diffuse adenocarcinoma histology. EBV( +) GC also has a unique epigenetic profile and mutational status with frequent mutations of PIK3CA, ARID1A and BCOR, and PD-L1 and PD-L2 amplifications, as well. The aim of this review is to highlight clinical significance of EBV( +) GC and prognostic role of EBV infection, and to determine potentially appropriate drug therapy for this disease.

11504 Background: Management of chemotherapy-induced nausea and vomiting (CINV) remains challenging. OLN might provide several benefits over APR which is current standard of care – particularly in terms of nausea control and cost effectiveness. However, sedation associated with recommended doses of olanzapine precludes its wide use in oncology practice. Methods: This was randomized phase II single center study aimed to compare OLN and APR in CINV prophylaxis. Key inclusion criteria were: chemo- and radio-therapy naïve patients, planned administration of high-emetogenic chemotherapy (cisplatin, carboplatin AUC≥4, doxorubicin etc). Patients were randomized 1:1 ratio in the following arms: olanzapine 5 QD day 0-4 or aprepitant 125 mg day 1, 80 mg day 2,3. All patients received ondansetron 16 mg day 1 and dexamethasone 8 mg day 1-3. Primary endpoint was complete nausea control (no nausea and no rescue medication) 0-120 hours after chemotherapy. Complete response (no emesis and no rescue medication) was a key secondary end point. Nausea was assessed using MASCC Antiemesis Tool. Sample size: 94 patients to increase nausea control rate from 40 to 70% (α = 0.05; β = 0.80; 10% of estimated data loss). Results: We included in the analysis 93 patients who could be evaluated. The groups were well balanced, median age was 49 years, vast majority of patients (95.6%) were females. The proportion of patients with complete nausea control in OLN and APR groups was 44.2% and 24.0% respectively (RR 2.5; 95% CI 1.04-6.08; p = 0.039). Complete response was achieved in 74.4% and 54.0% patients respectively (RR 2.48; 95% CI 1.026-5.99; p = 0.041). No differences in rates of undesired sedations were detected. Conclusions: Our data suggests superiority of OLN regimen in terms of nausea control. This regimen deserves further investigation. Clinical trial information: NCT03478605.

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