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Accurate diagnostic biomarker testing, including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2) expression profile, is crucial to appropriate management decisions in breast cancer. Receptor status testing is typically performed on the initial core needle biopsy (CNB) and surgical specimen (SS). The rate of concordance between CNB and SS is unclear as is the impact this has on clinical decision making. The current guidelines on retesting are vague, which results in individual institutions and providers determining retesting policies. Several studies worldwide have assessed the concordance of receptor testing with mixed conclusions. We aim to determine concordance between CNB and SS, and whether this leads to clinically relevant management changes. A retrospective analysis was performed on patients with invasive breast cancer with available CNB and SS pathology at our institution between January 2010- May 2020. Patients who were treated with primary surgical resection and neoadjuvant chemotherapy with residual disease were included. Concordance rates between CNB and SS were assessed for ER, PR, and Her2 IHC/ FISH amplification. ER and PR status were defined per NCCN guidelines as “positive,” “low-positive (ER)” or “negative.” Major discrepancy was defined as a change in label of “positive” or “negative”. Minor discrepancy was defined as change >10% without a “positive” or “negative” label change. Major discordance in Her2 was defined as change in label of “positive” or “negative” based on IHC or FISH amplification results. A minor discrepancy was a change in Her2 IHC (0-3) or FISH amplification without change in label of “positive” or “negative.” The clinical impact of discordant results was determined by investigator review. 748 patients met the eligibility criteria, and 64 of these patients received neoadjuvant therapy. For ER, there was 90.6% concordance, 2.2% major discordance, and 7.8% minor discordance between CNB and SS. For PR, there was 59.64% concordance, 11.9% major discordance, and 28.46% minor discordance. For Her2, there was 54.7% concordance, 1.6% major discordance, and 43.8% minor discordance. Of major discordance, ER (43.8%) led to the most change in management compared to Her2 and PR (12.5% and 2.2%, respectively). Retesting Her2 on SS did not change management when initial CNB was Her2 positive. For major discrepancies, patient demographics, tumor characteristics, treatment course, recurrence, and survival were reviewed. Although discordance was more common in PR and Her2 than ER biomarker profiles, major discordance leading to treatment changes were more common in ER and Her2. Retesting ER and Her2 on CNB and SS may be more clinically beneficial than retesting PR. Guidelines for retesting receptor profiles on CNB and SS are needed to best guide patient care management decisions that maximize clinical benefits while minimizing healthcare costs. Table: Concordance of ER, PR, and HER2 Expression ProfileConcordanceMajor DiscrepancyMinor Discrepancy# Patients with Change in Treatment with Major DiscrepanciesER90.6%2.2%7.8%7/16 (43.8%)PR59.6%11.9%28.5%2/90 (2.2%)Her254.7%1.6%43.8%5/12 (12.5%) Citation Format: Jessica Anne Slostad, Nicole Yun, Aimee Schad, Surbhi Warrior, Ruta Rao. Concordance of breast cancer biomarker testing in core-needle biopsy and surgical specimens: A single institution experience [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-34.

Patients with HER2-positive breast cancer have seen improved survival and outcomes over the past two decades. As patients live longer, the incidence of CNS metastases has increased in this population. The authors’ review outlines the most current data in HER2-positive brain and leptomeningeal metastases and discuss the current treatment paradigm in this disease. Up to 55% of HER2-positive breast cancer patients go on to experience CNS metastases. They may present with a variety of focal neurologic symptoms, such as speech changes or weakness, and may also have more diffuse symptoms related to high intracranial pressure, such as headaches, nausea, or vomiting. Treatment can include focal treatments, such as surgical resection or radiation (focal or whole-brain radiation), as well as systemic therapy options or even intrathecal therapy in the case of leptomeningeal disease. There have been multiple advancements in systemic therapy for these patients over the past few years, including the availability of tucatinib and trastuzumab-deruxtecan. Hope remains high as clinical trials for CNS metastases receive greater attention and as other HER2-directed methods are being studied in clinical trials with the goal of better outcomes for these patients.

Background The Coronavirus disease-2019 (COVID-19) is a global pandemic caused by novel coronavirus SARS-CoV-2. Acute respiratory and renal failure as well as systemic coagulopathy are critical aspects of the morbidity and mortality in patients with COVID-19. Heparin Induced Thrombocytopenia (HIT) occurs when IgG antibodies form against platelet factor 4-Heparin complex, resulting in platelet activation and removal, leading to a prothrombotic state. HIT is suspected when there is a platelet count decrease of more than 50% after exposure to heparin, along with hypercoagulability. Clinical Scoring systems like 4T Score (Thrombocytopenia, Timing, Thrombosis, no other cause of Thrombocytopenia) have been developed to assess the pretest probability of HIT. The use of unfractionated heparin, post-orthopedic and post-cardiac surgery state, female gender, and old age are recognized as risk factors for HIT. There is a nine-fold increased risk of developing HIT in patients requiring hemodialysis. ICU patients and patients with VTE without thrombocytopenia are considered to have low pre-test probability for HIT. Studies have shown that only 6% who are investigated serologically for HIT actually have the diagnosis. We conducted this study to assess the incidence and risk factors for HIT in COVID-19 positive patients and its impact on mortality. Methods A retrospective analysis was performed on all patients who were COVID-19 positive and hospitalized between March 1, 2020 and June 26, 2020 at our institution. Patients with intermediate or high suspicion for HIT, based on 4T score of 4 or higher, underwent IgG-specific platelet factor 4(PF4)-dependent enzyme immune assay (EIA). Washed platelet assays such as serotonin release assay (SRA) and heparin-induced platelet aggregation (HIPA) were used as confirmatory tests in cases with intermediate or low optical density (OD) with EIA. The incidence of HIT, its impact on mortality, and positivity of IgG-specific PF4-EIA in COVID-19 patients were studied, and statistical analysis was done with X2 testing. Subgroup analysis was performed based on demographic factors and risk factors for HIT, including exposure to heparin or low molecular weight heparin (LMWH), history of or cancer, recent orthopedic or cardiac surgery, exposure to renal replacement therapy (RRT), and severity of disease (D-dimer >6 ULN, Acute Kidney Injury, ICU admission, and mechanical ventilation requirement). These factors were analyzed by Fisher's exact test to determine their impact on mortality. The hospital course for HIT antibody-positive patients was further analyzed to study the impact of COVID-19 related therapy, such as Remdesivir, Tocilizumab, Hydroxychloroquine, Steroids, and anticoagulation after diagnosis of HIT. Results WEight out of 1265 hospitalized COVID-19 positive patients tested positive for IgG-specific platelet factor 4(PF4)-dependent enzyme immune assay (EIA+). Incidence of EIA+ in COVID-19 patients was 0.6%, which is significantly higher than in the general population 0.2% (p1, 1 was SRA positive) which is significantly higher than confirmation of HIT in nonCOVID-19 patients 6% (p Conclusion Our study indicates incidence of HIT is higher in the COVID-19 population. The incidence of positive EIA for patients with intermediate to high 4T scores is also higher in COVID-19 positive patients. This can be attributed to the cytokine storm and severe sepsis seen in critically ill COVID-19 patients. Our study also suggests that development of HIT can contribute to increased risk for thromboembolic events as well as mortality of COVID-19 patients, however, our study is limited due to small sample size. Therefore, prospective studies are needed to analyze the impact of HIT on morbidity, mortality and long-term outcomes in COVID-19 patients. Table Disclosures No relevant conflicts of interest to declare.

Background The Coronavirus disease-2019 (COVID-19) is a global pandemic. Acute respiratory compromise and systemic coagulopathy cause significant morbidity and mortality. Venous thromboembolism (VTE), which encompasses both deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as arterial thromboembolism (ATE), which includes stroke, are common sequelae described in this patient population. COVID-19 coagulopathy is attributed to severe inflammation and endothelial dysfunction resulting in a prothrombotic state. COVID-19 related treatment has focused on targeting the unregulated inflammatory state in an attempt to decrease incidence of COVID-19 related complications, such as thrombosis. Prophylactic anticoagulation is recommended, and many suggest intermediate to therapeutic anticoagulation in severe COVID-19. However, there is no clear data showing impact of anticoagulation on morbidity and mortality in patients with COVID-19. Methods A retrospective analysis was performed on all COVID-19 patients hospitalized between March 2020 and June 2020 at our institution. Patient charts were individually reviewed to ensure accuracy of data. Thromboembolic events (VTE or ATE) verified by imaging were included in the analysis. The impact of COVID-19 specific treatments such as Remdesivir, Tocilizumab, Hydroxychloroquine, and steroids on incidence of thrombosis was analyzed by using X2 testing. Using logistics regression, we analyzed the effect of prophylactic versus therapeutic anticoagulation received before development of thrombosis on mortality. Results Out of 1265 COVID-19 positive hospitalized patients during our time frame, 138 (10.9%) had thromboembolism. Incidence of 6.3% VTE, 5.6% DVT, 4.8% PE in COVID-19 patients was significantly higher than 0.24% VTE, 0.15% DVT, 0.12% PE in non COVID-19 hospitalized patients as reported by CDC (p Conclusion In Our study the incidence of thrombosis in hospitalized COVID-19 patients was significantly higher than non-COVID-19 hospitalized patients. COVID-19 patients with thrombosis had higher mortality compared to COVID-19 patient without thrombosis, particularly patients with PE. Hispanic patients with COVID-19 and thrombosis experienced a higher mortality rate compared to non-Hispanic patients. The lowest incidence of thrombosis occurred in COVID-19 patients who received steroids, followed by Tocilizumab suggesting that steroids and Tocilizumab may reduce the pro-inflammatory state leading to thrombosis. However, mortality rate was higher in patients who received COVID-19 related treatment, suggesting that these patients likely had severe disease. There was no mortality difference in patients who received prophylactic versus therapeutic anticoagulation prior to thrombosis. Randomized control trials will address the impact of anticoagulation dosing on morbidity and mortality in COVID-19 patients and study the post discharge prophylaxis and long-term outcomes in these patients. Disclosures No relevant conflicts of interest to declare.

Background Coronavirus disease-2019 (COVID-19) has become a global pandemic causing respiratory compromise, coagulopathy and renal failure in severe cases. Studies demonstrate a high incidence of venous thromboembolism (VTE), up to 69% in patients with severe COVID-19 infection. Coagulopathy in COVID-19 patients is attributed to excessive inflammation and endotheliopathy. Pregnant patients have approximately a 4-fold increase of VTE incidence. This is in part due to an increase in clotting factors and fibrinogen and a decrease in fibrinolytic activity and protein S. Increased stasis and the presence of acquired and inherited thrombophilias can contribute to increased VTE incidence during pregnancy and postpartum period (PP). Risk factors for thrombosis in pregnancy include African American race, heart disease, diabetes, smoking, multiparity, age >35 years, and obesity. Pregnancy/PP state and COVID-19 infection independently increase the risk of VTE which raises concern for an even higher incidence of thromboembolic events in pregnant/PP patients with COVID-19. Data pertaining to hypercoagulability in COVID-19 infected pregnant patients is currently limited. We conducted this study to evaluate the incidence of thrombosis and mortality in pregnant/PP COVID-19 positive patients. Methods A retrospective analysis was performed on all COVID-19 positive hospitalized patients between March 2020-June 2020 at our institution. Pregnant and PP patients were extracted from this cohort and individually chart reviewed by clinicians. Data from the Centers for Disease Control and Prevention on COVID-19 positive pregnant women in the United States from January 22-July 7, 2020 was utilized for comparison analyses. Statistical analysis was performed with chi-square testing. The incidences of thrombosis and mortality were compared between hospitalized COVID-19 positive pregnant/PP patients and hospitalized adult COVID-19 positive women of childbearing age (18-51 years). A subgroup analysis was performed to evaluate risk factors for thrombosis such as demographics, trimester of pregnancy, and single/multiple gestation (Table 1). Anticoagulation and COVID-19 related therapies administered in this cohort were also studied. Results Forty-three pregnant/PP COVID-19 positive patients were identified out of 1265 hospitalized COVID-19 positive patients at our institution. Thrombosis (DVT, PE, or stroke) incidence in our cohort was 0%, which was not significantly different compared to 6.12% incidence of thrombosis in hospitalized COVID-19 positive women of childbearing age (P = .097). The mortality rate of COVID-19 positive pregnant/PP patients was 0%, which was not significantly different compared to the mortality rate of 3.06% in hospitalized COVID-19 women of childbearing age (P = .25). Further, VTE incidence of 0% in hospitalized COVID-19 positive pregnant/PP patients was not significantly different from the 0.1% incidence of VTE in the non COVID-19 pregnant population in the United States (P=.84). Lastly, the 0% mortality rate in COVID-19 positive pregnant/PP patients at our institution was no different than the 0.0169% mortality rate of pregnant women without COVID-19 infections in the United States (P = .93). Conclusion Our study demonstrates no significant difference in incidence of thrombosis and mortality rate between hospitalized COVID-19 positive pregnant/PP patients and hospitalized COVID-19 positive women of childbearing age. There was also no difference in VTE incidence between hospitalized COVID-19 positive pregnant/PP patients and non COVID-19 pregnant women in the United States. The lack of significant difference in both thrombosis incidence and mortality rate in patients who are both COVID-19 positive and pregnant/PP is reassuring and may imply that pregnancy might play a role in decreasing the inflammatory response of COVID-19. During certain phases of pregnancy a high number of macrophages, natural killer cells, and T regulator cells in the decidua have been identified, which could indicate an overall increased systemic immune response, potentially decreasing the dysregulation of the cytokine storm seen in critically ill COVID-19 patients. However, the systemic immunologic changes in pregnancy and the postpartum period remain largely unknown and prospective studies are needed to further investigate the effects of COVID-19 on pregnant patients. Disclosures No relevant conflicts of interest to declare.

Background The virus SARS-CoV-2, which causes COVID-19 has rapidly spread into a global pandemic. In critically ill patients with the disease, common symptoms include sepsis, severe pneumonia with acute respiratory distress syndrome (ARDS), and complications such as coagulopathy and thrombosis. Many patients with COVID-19 have sequelae such as venous thromboembolism (VTE) including pulmonary embolism (PE) and deep vein thrombosis (DVT) as well as arterial thromboembolism (ATE) including stroke. COVID-19 induced inflammation can induce a prothrombotic state by activating the coagulation cascade; coupled with the immobility of severe and critically ill patients in ICU, making thrombosis common in this patient population. Different blood types in patients include A, B, AB, and O. ABO carbohydrate moieties are genetically inherited and have been linked to predisposing patients to cardiovascular diseases, cancers, and even susceptibility of COVID-19. Blood type positivity and negativity are determined by the Rhesus (Rh) factor, which is a protein found on the surface of red blood cells and is also genetically inherited and linked to higher incidence of certain diseases such as diabetes. Studies have shown a relationship between blood types and increased severity of infection from COVID-19 including increased risk of thrombosis. Blood type A has been shown to have higher severity of disease with O blood type having a lower risk of infection or mortality. This study was done to evaluate if patients with different blood types have increased risk for thrombosis or higher mortality rates with COVID-19 infection. Methods A retrospective analysis was performed on COVID-19 positive hospitalized patients between March 1, 2020 and June 26, 2020 at our institution with reported blood typing. Patients who had a thromboembolism (VTE, DVT, PE, ATE, or stroke) verified by imaging were extracted from this cohort and included in the analysis. The prevalence of different blood types in COVID-19 patients was compared to the general population without COVID-19. The incidence of thrombosis and mortality rate based on blood type was analyzed to understand severity of COVID-19 disease. Statistical analysis was performed using chi-squared testing. Results Among 1265 COVID-19 positive patients during our time frame, 138 patients were identified to have a thrombosis. Of those, 102 patients with thrombosis and 402 without thrombosis had reported blood types that were used for analysis. There was no significant difference in prevalence of blood types in COVID-19 patients (A 34.3%, AB 2.9%, B 16.7%, O 46.1%) to the general nonCOVID-19 population (A32.7%, AB 4.2%, B 14.9%, O 48.1%) (p=0.8572). There was no significant difference in incidence of thrombosis between blood types: A (23.3%), AB (15%), B (20.7%), and O (18.7%) (p=0.6513). When stratifying by Rh factor, there was also no significant difference in incidence of thrombosis by blood types: A- (11.1%), A+ (24.1%), AB- (0%), AB+ (15.8%), B- (25%), B+ (20.3%), O- (18.2%), O+ (18.7%) (p=0.9054). There was also no significant difference in mortality rate between COVID-19 patients based on blood types in our cohort: A (20.7%), AB (15%), B (13.4%), and O (21.8%) (p=0.3747). Conclusion Our study demonstrates that there is no increased prevalence of one blood type over another between COVID-19 patients compared to the general population, showing that patients are not at higher risk for COVID-19 infection based on blood type. There was also no difference between blood types based on incidence of thrombosis. When further stratifying with Rh factor, there was also no difference in incidence of thrombosis based on blood types. This shows that regardless of Rh positivity or negativity, there is no increased risk for thrombosis in COVID-19 patients based on blood type. There is also no difference in mortality in COVID-19 patients based on blood type. Since COVID-19 patients who are critically ill and have more severe disease have higher incidence of thrombosis and higher mortality rates, our study suggests that patients are not at higher risk for severe COVID-19 disease based on blood type. However, this study is also limited due to small sample size, and prospective studies are needed to better understand the relationship between blood type and severity of disease in COVID-19+ patients. Disclosures No relevant conflicts of interest to declare.

e12518 Background: Oncotype dx is a 21 gene breast cancer assay that helps predict benefit of chemotherapy in early-stage hormone receptor positive (HR+), HER2 negative, 0 to 3 node positive breast cancer as reported by TAILORx and RxPonder trials. Both trials found no benefit of adjuvant therapy in mid-range scores of 11-25 with the exception of some benefit in age under 50 or premenopausal status, no benefit if score was 0-10, and benefit of chemotherapy if >25. Methods: All breast cancer patients between 2019-2020 were chart checked to evaluate oncotype dx scores. Patient characteristics were analyzed between oncotype dx scores of 0-10, 11-25, and >25 using X square tests. 2000-2020 institutional cancer registry data was analyzed to understand recurrence and mortality in patients with oncotype dx testing. Results: 173 patients had oncotype dx testing between 2019-2020, and most were HR+, HER2-, and had 0-3 lymph nodes. There was no difference in race or ethnicity between the groups of oncotype dx scores (Table), and average age at diagnosis for all three groups was 58 years. More patients with lower oncotype dx score had hormone therapy, but this was not significant (0-10 at 93.6%, 11-25 at 90.8%, and >25 at 82.1%, p=0.26). Patients with a higher oncotype score were significantly more likely to have chemotherapy (0-10 at 0%, 11-25 at 17.3%, and >25 at 82.1%, p25 at 2.1% (p=0.15). The recurrence was highest in the 0-10 group at 5.4%, but not significant compared to the 11-25 group at 4.1% and >25 group at 4.2% (p=0.09). Conclusions: Race, ethnicity, and age does not impact predisposition to high oncotype dx score, which is interesting since literature shows minority women have higher mortality rates. This could be because oncotype dx looks at early-stage breast cancers and many minority women have later stages at diagnosis. There was no difference in which group received hormone therapy and there was significantly higher rate of chemotherapy administration in patients with scores >25, which is consistent with prospective trial recommendations. When evaluating long term outcomes between oncotype dx groups over 20 years, there was no significant difference in recurrence of disease or mortality indicating that oncotype dx scoring accurately predicted overall benefit of chemotherapy.[Table: see text]