Background Hypercoagulability may contribute to COVID‐19 pathogenicity. The role of anticoagulation (AC) at therapeutic (tAC) or prophylactic doses (pAC) is unclear. Objectives We evaluated the impact on survival of different AC doses in COVID‐19 patients. Methods Retrospective, multi‐center cohort study of consecutive COVID‐19 patients hospitalized between March 13 and May 5, 2020. Results A total of 3480 patients were included (mean age, 64.5 years [17.0]; 51.5% female; 52.1% black and 40.6% white). 18.5% (n = 642) required intensive care unit (ICU) stay. 60.9% received pAC (n = 2121), 28.7% received ≥3 days of tAC (n = 998), and 10.4% (n = 361) received no AC. Propensity score (PS) weighted Kaplan‐Meier plot demonstrated different 25‐day survival probability in the tAC and pAC groups (57.5% vs 50.7%). In a PS–weighted multivariate proportional hazards model, AC was associated with reduced risk of death at prophylactic (hazard ratio [HR] 0.35 [95% confidence interval {CI} 0.22‐0.54]) and therapeutic doses (HR 0.14 [95% CI 0.05‐0.23]) compared to no AC. Major bleeding occurred more frequently in tAC patients (81 [8.1%]) compared to no AC (20 [5.5%]) or pAC (46 [2.2%]) subjects. Conclusions Higher doses of AC were associated with lower mortality in hospitalized COVID‐19 patients. Prospective evaluation of efficacy and risk of AC in COVID‐19 is warranted.

No abstract

1537 Background: Heterozygous germline ATM mutation carriers have an increased risk of developing breast, pancreas, and other cancers. The clinical and pathologic characteristics of ATM-associated breast cancers have not been well defined. Methods: Patients who underwent multigene panel testing (MGPT) between 2013-2019 and identified to harbor ATM mutations were included in the study. We evaluated demographics, pathology, and surgical management of our ATM mutation carriers with breast cancer. Results: At total of 319 individuals were identified to have variants in ATM, of which 114 were pathogenic/likely pathogenic. The majority of patients were female (82%) and Caucasian (88%). A total of 56 patients (49%) had a personal cancer diagnosis, the most common of which was breast cancer (n = 39). Nine individuals had more than one primary malignancy. The mean age at breast cancer diagnosis was 52, with a range of 25-82. The majority of patients had invasive ductal carcinoma (74%), grade 2 or 3 (90%), and ER and /or PR positive (87%). Of those with known HER2 status, 24% were positive. Thirty-nine percent of patients were lymph node positive, and 42% had lymphovascular invasion. The most common stage at diagnosis was 2 (53%). Of the 39 mutation carriers with breast cancer, 16 (42%) received radiation therapy, and 16 underwent bilateral mastectomy. Of 114 ATM positive patients, there were 55 distinct variants. Sixteen (14%) individuals had a mutation in additional cancer predisposition genes. One variant, c.5015delG, was identified in ten patients in a large, consanguineous Iraqi family with an extensive history of pancreatic and other cancers. Eight individuals were identified to have the known high-penetrance variant, c.7271T > G. Conclusions: Our study describes the clinical and pathological characteristics of ATM mutations carriers with breast cancer. The majority of patients had intermediate to high grade disease, hormone receptor positive, with a suggestion of a higher rate of HER2 positivity and lymph node involvement. Additional studies are needed to elucidate the unique characteristics of ATM-associated breast cancer, which may have implications for personalized management.

1529 Background: Multigene panel testing (MGT) is commonly utilized in patients with a personal or family history of cancer. One of the more common gene mutations identified is in the ATM gene, associated with a moderately increased risk of breast and other cancers. There are reports of an association with pancreatic cancer, however the exact risks are unclear. The aim of this study is to describe the family history of pancreatic cancer in a cohort of ATM mutation carriers, and to evaluate possible genotype/phenotype correlation. Methods: Patients who underwent MGT, between ‘13 and ‘19, and tested positive for a pathogenic/likely pathogenic ATM mutation were included in this study. Family history, with a focus on pancreatic cancer, and genetic testing results were analyzed. Results: A total of 114 patients were identified to carry an ATM mutation. Twenty-two (19.3%) individuals had a family history of pancreatic cancer in a close relative, and of those, 13 (11.4%) had an affected first degree relative, and 11 (9.6%) had an affected second degree relative. Among the families with pancreatic cancer, 20 close relatives had a personal history of pancreatic cancer, with the youngest diagnosed at age 40, the oldest diagnosed at age 91, and a mean age of diagnosis of 66.5 years. Thirteen unique variants were identified: 4 splice site, 3 missense, 3 frameshift, 1 nonsense, and 1 silent. Two families had the known high-penetrance ATM mutation, c.7271T > C (p.V2424G). Conclusions: This study describes the association of pancreatic cancer in individuals found to carry pathogenic ATM mutations. A significant proportion (19.3%) of patients had a family history of pancreatic cancer in a close relative, diagnosed as young as age 40. The mean age of diagnosis was slightly younger than the average age in the general population (age 70). As pancreatic cancer screening continues to improve, this information will be an important component to help guide cancer risk assessment and future screening recommendations for ATM mutation carriers. Additional larger studies are needed to further characterize pancreatic cancer risks in patients with ATM gene mutations.