Background The SARS-CoV-2 pandemic has caused over 400,000 deaths worldwide thus far, and poses therapeutic challenges for millions of patients. There is currently no treatment for SARS-CoV-2 infection approved by the United States Food and Drug Administration. Multiple agents have been used off-label to treat SARS-CoV-2 infection based on small observational cohorts and in vitro data. Here we present the experience of a large academic medical center in treating SARS-CoV-2 infection. Methods We performed a retrospective cohort study of patients admitted for greater than 24 hours with a nasopharyngeal, oropharyngeal, and/or bronchoalveolar lavage sample positive for SARS-CoV-2 by polymerase chain reaction (PCR). Demographic data, comorbidities, clinical data, and treatment data were collected from the electronic medical record. Off-label therapies were used at the discretion of the treating providers guided by regularly updated treatment guidelines assembled by infectious diseases physicians and antimicrobial stewardship pharmacists. The primary outcome assessed was in-hospital mortality. Secondary outcomes included admission to the intensive care unit (ICU), endotracheal intubation, initiation of vasopressors, and drug-related adverse events. Results Data collection was completed for 448 patients admitted between March 18, 2020 and May 8, 2020. All-cause in-hospital mortality was 13.4% (60/448) during this time. Mortality rates increased with age, up to 45% for patients over 80 years old. Male sex, hypertension, chronic pulmonary disease, end-stage renal disease, chronic liver disease were also risk factors for increased mortality. QTc interval prolongation occurred significantly more frequently in patients who received hydroxychloroquine (HCQ) with or without azithromycin(AZM) than those who did not (HCQ 6%, HCQ+AZM 7.8% vs all other patients, 0%, p< .0001). Review of treatment trends showed close adherence to the treatment recommendations at that time (Figure 1). Patient Characteristics Admission Laboratory Data by Disease Severity QTc Prolongation Conclusion SARS-CoV-2 infection is associated with significant inpatient mortality, and use of off-label treatments was associated with significant drug-related adverse events. Treatment regimens changed rapidly, and providers adhered closely to institutional guidelines as they evolved. Treatment Trends by Week QTC pre/post Treatment by Hydroxychloroquine Use vs. No Hydroxychloroquine Use Disclosures Samir Gupta, MD, Gilead Sciences (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member)ViiV (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support)

Breast cancer care in the developing world is limited by access to quality ER and HER2 IHC diagnostic assays needed to justify hormone and HER2 therapeutics. Shipping pathology specimens to a central testing site often out of country delays therapy and is costly. The Xpert Breast Cancer Stratifier assay makes quantitative measurements of ESR1, PGR, ERBB2, and MKi67 mRNAs from FFPE specimens in <2 hours on an easy-to-use automated diagnostic platform, the GeneXpert (GX). 10,000 GX machines are currently in use in 182 countries offering the possibility of a point-of-care solution. We compared concordance in tumor samples between IHC and mRNA intending to challenge the limits of the GX mRNA assay. 83 breast tumor samples were chosen including those with low cellularity, small volume disease, unusual subtypes, ER- tumors with surrounding benign epithelium, and low level HER2+ tumors. mRNA, IHC and FISH assays were performed. Slides were tested following macrodissection of invasive carcinoma and as non-macrodissected whole sections. GX measurements for Ki67 were compared with mitotic rate as an alternative to Ki67 IHC. Overall percent agreement following macrodissection was 95% for ER, 89% for HER2, 76% for PR, and 80% for Ki67 (>20% positive cut), and using whole section, 99% for ER, 80% for PR, 92% for HER2, and 73% for Ki67. Concordance was 92% for both macrodissection and whole section using mitotic rate to assess proliferation. Ignoring HER2 2+ calls which represented low level amplified tumors by FISH, the concordance rates were 95% for macrodissection and 99% for whole section. Discordance when testing long-term stored 4μm sections was resolved in a number of cases by using a fresh cut from the FFPE block. Half the ER discrepancies were in very small volume tumors ≤25mm2 and 75% were classified as ER-ve by IHC, and positive by Stratifier. 80% of ER IHC- cases were appropriately identified as ER- by the Stratifier in the presence of benign breast epithelium. HER2+ DCIS adjacent to HER2- invasive tumor resulted in a discrepant HER2 mRNA result even with macrodissection. No ER or HER2 discrepancies occurred in low cellularity tumors (≤30% cellularity) nor in lobular and mucinous subtypes. In a study intended to challenge an mRNA breast biomarker assay, concordance between mRNA results and IHC was high for ER and HER2, the two most important prognostic markers needed for therapeutic decision making. Use of whole sections rather than tumor macrodissection did not decrease concordance. Discrepant ER cases were more prevalent when analyzing low volumes of tumor and in this setting were seen in ER IHC- tumors surrounded by ER+ normal epithelium, or with weak IHC expression, highlighting predictable limitations of the assay. Concordance was better between Ki67 mRNA and mitotic rate than with IHC. Re-test data suggested that a fresh cut of the FFPE block yields the best results by GX, perhaps due to mRNA degradation in stored 4μm sections. The Xpert Breast Cancer Stratifier may provide a rapid, cost-effective solution to the problem of obtaining accurate diagnostic results at the point-of-care in low resource settings, and deserves further evaluation in developing countries. Citation Format: Brock JE, Milner DA, Ho K, Natalie W, Victor C, Annaliza R, Teresa B, Kathryn G-F, Edwin LW, Jodi W, Wendy W, Michael B. Comparison of the Xpert breast cancer stratifier mRNA assay with central ER, PR, HER2, and Ki67 immunohistochemistry (IHC) for rapid biomarker analysis in developing countries [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-07.

Background: Population-based estimates in the United States indicate that uptake of breast cancer chemoprevention has remained low despite more than a decade of scientific evidence demonstrating clinical benefit. The objective of our study was to evaluate the uptake of breast cancer chemoprevention in a high-risk clinical setting. Methods: We evaluated the uptake of chemoprevention (tamoxifen, raloxifene or exemestane) 2007 to 2011 among 1,151 healthy women at high risk of breast cancer who were seen at the MD Anderson Cancer Center and enrolled in a high-risk breast cancer cohort. We used stepwise multivariable logistic regression to determine patient-related factors associated with use of chemoprevention. Results: Mean age of the cohort was 60 years; 85% of the women were white, 6% black and 9% of other ethnicities. Chemoprevention use was reported among 29% of women (n=340) (22% tamoxifen, 7% raloxifene). Among women with a history of lobular carcinoma in situ (LCIS), a proliferative breast lesion or Gail 5-year risk ≥1.66%, the uptake of chemoprevention was 52%, 42% and 14%, respectively. In multivariable analysis, history of osteoporosis (p=0.0034), prior use of hormone replacement therapy (p=0.0002) and elevated Gail model 5 year risk >3.0% (p=0.003) were positively associated with uptake of chemoprevention. Conclusion: Women seen in a high-risk clinical setting may be more motivated to use chemoprevention and uptake was highest among women with a history of LCIS or a proliferative breast lesion. Individualized strategies are needed to improve breast cancer chemoprevention uptake among different subsets of high-risk patients. Citation Format: Scott Nimmons, Arvind Bambhroliya, Bevers Teresa, Jun Ying, Powel Brown, Elise Cook, Lonzetta Newman, Abenaa Brewster. The evaluation of breast cancer chemoprevention uptake in a high-risk cohort. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B17.