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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Concentration of spermine (87 ± 13 μM) and citric acid (45 ± 4 mM) in prostatic fluids from 44 men were highly significantly correlated (r = 0.795). It was concluded that both probably arise from the same exocrine cell.

Background: Patients with interstitial lung disease (ILD) are at high risk of severe COVID-19 infection. Additionally, their anti-inflammatory and antifibrotic treatment may cause immunosuppression. Nevertheless, their ability to mount an adequate immune response to messenger RNA SARS-CoV-2 vaccines was not evaluated. We aimed to evaluate the humoral response after the BNT162b2 vaccine among idiopathic pulmonary fibrosis (IPF) patients treated with antifibrotic therapy and among non-IPF ILD patients treated with anti-inflammatory therapy.Methods: We conducted an observational prospective cohort study to evaluate the rate of anti-spike (S-IgG) antibodies after two doses of the BNT162b2 vaccine in patients with ILD. The cohort included 40 patients with idiopathic pulmonary fibrosis (IPF) treated with anti-fibrotic therapy and 29 patients with non-IPF ILD treated with anti-inflammatory therapy. For S-IgG titer measurement one serology test was drawn from all patients 4-6 months after the second vaccine dose. Two age and sex matched control groups were created from a healthy control cohort of 107 patients. The study was conducted in Rabin Medical Center (Israel) between June to August 2021.Results: All patients in the anti-fibrotic arm were seropositive (40/40), corresponding to the matched control group (P=1.0). The antifibrotic arm had a significantly lower median antibody titer in comparison to the matched control group (361.10 [ IQR, 207-811] AU/ml vs 820.75 [IQR, 459-1313] AU/ml; P<0.001). Only 48.3% (14/29) of patients in the anti-inflammatory arm were seropositive in comparison to 100% (29/29) in the healthy control group (P<0.001). The anti-inflammatory arm had a significantly lower median antibody titer in comparison to the healthy control group (39.6 [ IQR, 4.25-165] AU/ml vs 970.1 [IQR, 505-1926] AU/ml; P<0.001). Conclusion: IPF patients treated with antifibrotic therapy mount an adequate immune response after 2 doses of the BNT162b2 vaccine, maintain a 100% seropositivity rate, 4-6 months after vaccination. However, their antibody titer was reduced in comparison to a healthy control group. Among patients with non-IPF ILD, treated with anti-inflammatory therapy, 48% were seronegative 4-6 months after the second vaccine dose, moreover treatment with rituximab caused significant immunosuppression, even in comparison to other anti-inflammatory treatments.

e13011 Background: Trastuzumab is a monoclonal antibody that targets the human epidermal growth factor receptor-2 (HER2). Its use may result in cardiotoxicity. There are no formal guidelines for left ventricular ejection fraction (LVEF) monitoring in patients with metastatic disease treated with trastuzumab. Our local guideline include an echocardiogram every 3 months for these patients. Methods: We collected data from electronic records and hard copy files of patients treated with Trastuzumab as first line, between the years 2011-2014. Results: One hundred patients met the inclusion criteria. Median treatment duration of all patients was 30 months, with an average of 12 echocardiogram follow-ups per patient. Ninety-nine patients (99%) received additional chemotherapy. Thirty patients (30%) also received Pertuzumab. Ten (10%) of the eligible 100 patients showed significant decline in EF (≥10%) to a final LVEF of < 50%. The median follow-up duration of these patients was 52 months. Median EF at the beginning of treatment was 61.5% in all patients. Cardiotoxicity occurred at an average of 23 months [median 18 months] after beginning of Trastuzumab treatment (range; 3-54 months), with an average EF decline of 14% (range; 10-18%). Three patients (30%) required treatment change due to the decline in EF. Temporary cessation of treatment was necessary in 4 (40%) of the patients for a period of time between 4 weeks to 8 months. The remaining 3 patients (30%), although developing significant decline in EF, did not require treatment cessation or change. None of the 10 patients presented any other clinical sign of cardiotoxicity. In the group with cardiac events, there were no previous reports of congestive heart failure (CHF), ischemic heart failure (IHF), myocardial infraction (MI) or diabetes. Only one patient was a smoker and another received hormone replacement therapy. The average age of this group at the time of diagnosis of metastatic disease was younger (50.6 vs. 55.8, P-value 0.5). Conclusions: Monitoring heart function by trimonthly echocardiogram does not seem to be the optimal monitoring modality in metastatic breast cancer patients who receive a trastuzumab-containing regimen as first line. This study results suggest that less frequent monitoring may be sufficient, thus diminishing patients' inconvenience and allowing better allocation of health care resources.