Background: Recent data suggest that human epidermal growth factor receptor 2 (HER2)-low breast cancer may represent a distinct entity. We aimed to compare disease characteristics and outcomes between HER2-low and HER2-0 in estrogen receptor (ER) positive, early-stage breast cancer. Methods: A single center retrospective study comprising all women with ER positive, HER2 negative early breast cancer, for whom an Oncotype DX test was performed between 2005 and 2012. Women were grouped to HER2-low (immunohistochemistry þ1 or þ2 and in situ hybridization not amplified) or HER2-0. Clinico-pathological features and Oncotype recurrence score (RS) were collected. Data on overall-survival (OS), disease-free survival (DFS) and distant disease-free survival (DDFS) were evaluated according to HER2 expression status. Results: 608 women were included, of which 304 women had HER2-0 and 304 had HER2-low disease. Lobular subtype was significantly more common in HER-0 compared to HER2-low disease (17% vs. 8%, p ¼ 0.005). The prevalence of other clinic-pathological characteristics and long-term prognosis were comparable between both groups. For women with high genomic risk (RS > 25), HER2-low expression was associated with significantly favorable OS (HR ¼ 0.31, 95% CI 0.11e0.78, p ¼ 0.01), DFS (HR ¼ 0.40, 95% CI 0.20e0.82, p ¼ 0.01) and DDFS (HR ¼ 0.26, 95% CI 0.11e0.63, P ¼ 0.002) compared to women with HER2-0. For women with low genomic risk (RS 25), long-term prognosis was unrelated to HER2 expression. Conclusion:The prognostic impact of HER2-low expression in early-stage luminal disease varies across the genomic risk, with significant favorable outcomes of HER2-low expression compared to HER2-0 in women with high genomic risk.

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Objective: Gastric cancer (GC) is a leading cause of cancer death, occurs predominantly in older age, with increasing incidence in young patients. The Cancer Genome Atlas indicates four subtypes for GC among which Epstein-Barr virus (EBV) subtype is estimated at 8.7%. We aim to determine the prevalence of EBV subtype in young GC patients (≤45 years) compared with an average-onset cohort (≥55 years) and characterize the clinicopathologic pattern of young-onset GC. Methods: Gastric cancer samples of patients of both cohorts were screened for EBV by qPCR. Additional staining was done for Human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI) status and Programmed death-ligand 1 (PD-L1). Demographics and clinical data were retrieved from the medical records. Results: Thirty-nine young-onset and 35 average-onset GC patients were reviewed. There was no apparent difference in tumor location, family history, histology and HER2 status between the cohorts. More young-onset patients were diagnosed with metastatic disease (27% vs 9%, p = 0.0498). EBV was significantly more prevalent in the young-onset cohort (33% vs 11%, p = 0.025). 15/17 EBV positive patients were under the median age of diagnosis for GC in the US (68 years). MSI-H was found only in the average-onset cohort [0% vs 27%, p = 0.001). PD-L1 positivity was higher in the young-onset cohort (31% vs 3%, p = 0.002). Conclusion: Our study indicates that EBV subtype is more prevalent in young-onset GC and may play a key role in the pathogenesis. Higher rate of PD-L1 positivity in young-onset GC could change treatment strategies. We are currently evaluating these findings in a prospective trial.

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