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Background: Preliminary studies have characterized potential adverse effects associated with COVID-19 vaccination in pts with cancer. However, biological characterization of vaccine response has yet to be performed. Methods: Eligible pts with advanced GU cancers (metastatic/unresectable prostate, bladder and renal cell carcinoma [RCC]) and had not yet received COVID-19 vaccination. Pts were consented to receive sequential blood draws prior to vaccination and at landmarks of 2, 6, and 12 mos following vaccination. Pts on systemic treatment had additional blood draws coinciding with their first 3 cycles of therapy following vaccination. Ab titers to SARS-CoV-2 were quantified via ELISA and reported as an immune status ratio (ISR). RNA was extracted from PBMC aliquots, converted into cDNA and TCR α/β sequences were selectively amplified. TCR abundance and homology clustering was performed using custom scripts. Results: As of May 14, 2021, 130 pts had consented to the study of whom 126 pts submitted baseline (BL) specimens. The current analysis focuses on 56 pts who submitted cycle 1 (C1) specimens. Among these, 29, 26, and 1 pts had RCC, prostate and bladder cancer, respectively;19 were on checkpoint inhibitor (CPI)-based regimens while 37 were on non-CPI regimens. BNT162b2 (Pfizer) was the most commonly administered vaccine in the cohort (n=29), followed by mRNA-1273 (Moderna;n=26). COVID-19 Ab titers increased significantly from BL to C1 across the cohort from 0.19 (interquartile range [IQR] 0.12-0.18) to 4.37 (IQR 0.2-6.60;P

Background The predictors of recurrence in ER- DCIS and the role of tumor microenvironment (TME) is unclear. Correlation of clinico-pathologic features of ER- DCIS with molecular markers and PD-L1 expression has not been done. Therefore, we under took this retrospective study comparing the clinical outcomes between ER+ and ER- DCIS and correlated this with the expression of PD-L1 in the tumor cells and the Tumor infiltrating lymphocytes. We hypothesize that increased expression of PD-L1 in ER- DCIS and TILs predict recurrence. The aim of this study was to identify biomarkers in ER- DCIS associated with increased risk of recurrence or progression to metastatic disease. Methods 50 patients with ER+ and ER- DCIS were identified retrospectively. Clinico-pathologic data was correlated with survival outcomes and local or distant recurrence. Information collected was the size, margin status, nuclear grade, ki-67 expression, architectural pattern, necrosis, and molecular phenotype. 25 cases of ER- DCIS are presented in the abstract. The rest will be presented at the meeting. ER+ and ER- DCIS will be stained for PD-L1, and lymphocyte markers CD3, CD4, CD8, FoxP3, and CD20 for the TILs in ER+ and ER- DCIS. The clinical, radiological and Immuno-pathologic features of ER+ DCIS will be compared with ER negative DCIS. Results 3/25 (12%) had disease recurrence. Two (67%) had recurrence with metastatic triple negative breast cancer with brain, hepatic and osseous metastasis within 5 years. High grade was associated with the development of systemic disease. 1/3 (33%) had recurrence as ER negative DCIS. 2/3 (67%) had recurrence as ER+ tumor. The rate of recurrence and distant metastasis was seen to be higher in high grade ER negative DCIS. Conclusions ER- DCIS has an aggressive phenotype and a distinct biology. It is more likely to present as loco-regional or metastatic disease. Identification of genomic biomarkers, PD-L1 analysis in the tumor and the TILs is currently being undertaken. The molecular drivers and immunologic markers of recurrence in ER negative DCIS continue to be an active area of exploration. Further characterization of ER- DCIS immune microenvironment may identify useful targets for immune-based therapy and breast cancer prevention. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.