Patients with cancer experience higher burden of SARS-CoV-2 infection, disease severity, complications, and mortality, than the general population. SARS-CoV-2 mRNA vaccines are highly effective in the general population; however, few data are available on their efficacy in patients with cancer. Using a prospective cohort, we assessed the seroconversion rates and anti-SARS-CoV-2 spike protein antibody titers following the 1 st and 2 nd dose of BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines in patients with cancer in U.S. and Europe from January to April 2021. Among 131 patients, most (94%) achieved seroconversion after receipt of 2 vaccine doses. Seroconversion rates and antibody titers in patients with hematological malignancy were significantly lower than those with solid tumors. None of the patients with history of anti-CD-20 antibody in the 6 months prior to vaccination developed antibody response. Antibody titers were highest for clinical surveillance or endocrine therapy groups and lowest for cytotoxic chemotherapy or monoclonal antibody group.

Background The Next Accreditation System (NAS) increases the focus on educational outcomes and meaningful evaluation of learners. This requires that key clinical faculty develop new assessment formats such as entrustable professional activities (EPAs). Objectives To build and develop milestone-based assessment tools supporting 5 EPAs for a hematology/oncology fellow continuity clinic, and to educate key clinical faculty regarding the Clinical Competency Committee (CCC) and the NAS. Methods Program directors from 2 hematology/oncology fellowship programs developed 5 EPAs for continuity clinic evaluation supported by milestone-based assessment. The program directors met to create a unified CCC charter. Key clinical faculty helped to develop a milestone-based evaluation of fellow continuity clinic through creation of 5 hematology/oncology-specific EPAs. Formal entrustment regarding EPAs was deliberated by the CCC. Results A total of 18 fellows were evaluated. Clinical Competency Committee deliberation at each institution took approximately 10 minutes per fellow for discussion and decision regarding entrustment for all 5 EPAs supporting continuity clinic. One-third of postgraduate year (PGY)–4s, 50% of PGY-5s, and 100% of PGY-6s were deemed competent in all 5 EPAs by the CCC. Conclusions All hematology/oncology trainees in San Antonio were evaluated using milestone-based assessment for continuity clinic, and entrustment decisions regarding 5 EPAs were made by the CCC. This project may provide other programs with a sound basis for adoption and further development of the next generation of evaluation tools at their institutions. Entrustable professional activities that are rotation specific should be used as a starting point for linking to the competencies, subcompetencies, and the reporting milestones.

Unlike estrogen receptor α (ERα) that predominantly promotes hormone-dependent breast tumor growth, ERβ exhibits antitumor effects in a variety of cancer types. We recently identified a phosphotyrosine residue in ERβ, but not ERα, that dictates ERβ transcriptional activity and antitumor function. We show here that this ER isotype-specific phosphotyrosine switch is important for regulating ERβ activity in cell proliferation, migration, and invasion. At the mechanistic level, phosphorylated ERβ, which recruits transcriptional coactivator p300, is in turn targeted by p300 for ubiquitination and proteasome-dependent protein turnover. Furthermore, ERβ-specific agonists such as S-equol enhance ERβ phosphorylation, suggesting a crosstalk between ligand- and posttranslational modification-dependent ERβ activation. Inhibition of xenograft tumor growth by S-equol is associated with reduced tumor Ki-67 expression and elevated ERβ tyrosine phosphorylation. Taken together, our data support the notion that phosphotyrosine-dependent ERβ signaling is an attractive target for anticancer treatment.

BACKGROUND: Sacituzumab Govitecan (SG, TRODELVY™) is an FDA approved antibody drug conjugate for treatment of metastatic triple negative breast cancer (TNBC). SG has payload and linker characteristics preferable for CNS delivery including a pH hydrolysable, a payload (SN-38) that is the active 1000-fold more potent than the parent compound CPT-11 and crosses the blood brain barrier. Our preliminary data showed SG activity in intracranial xenografts leading to our hypothesis that SG would achieve concentration of SN-38 within the breast cancer brain metastases (BCBM) that would be therapeutically relevant. METHODS: We undertook a single center, prospective, window of opportunity trial (NCT03995706) to examine the concentrations of SG, SN-38, and SN-38G in tumors patients undergoing craniotomy for BCBM (n=20) or recurrent glioblastoma (rGBM, n=10). A single dose of SG was administered at 10mg/kg IV the day prior to craniotomy. Tumor was collected and [SN-38] was analyzed via mass spectrometry (UHPLC-HRMS). following recovery patients resumed SG at 10mg/kg IV days 1 and 8 of 21 day cycle and were assessed for response or progression every third cycle by MRI. RESULTS: To date 21 patients have been treated, including 11 BCBM and 10 rGBM. UHPLC-HRMS analysis was performed in the first 10 tumors (n=4 and 6 respectively). For BCBM, total concentration of SN-38 varied from 173nM to 1160nM, with a mean concentration of 626nM. All GBM patients had residual measurable disease and 4 breast patients had measurable disease. With a median follow-up of 12 weeks from the first postoperative cycle in the first 14 patients, 2 partial responses from each group were observed (ORR of 28% and 50% at 12 weeks respectively). Updated results will be presented. CONCLUSIONS: SG achieves therapeutically relevant concentrations of SN-38 at 150-fold mean IC50s for BCBM. Early intracranial responses are encouraging and merit further evaluation. A multi-center trial of SG for HER2 negative BCBM (SWOG S2007) will be enrolling soon. Citation Format: Andrew J Brenner, Renu Pandey, Jennifer Chiou, John Floyd, Prathiba Surapreneni, Virginia Kaklamani, Kate Lathrop, Richard Crownover, Stefano Tiziani. Delivery and activity of SN-38 by sacituzumab govitecan in breast cancer brain metastases [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 PD13-05.

Hispanic women and Non-Hispanic white women with breast cancer treated at an NCI-designated cancer center had similar times to biopsy and treatment initiation. These findings suggest that in majority minority communities with large cancer centers, racial disparities can be reduced. With a growing Hispanic population throughout the United States, future studies should examine the long-term impact on improved breast cancer survival in this population.