Despite new therapies, breast cancer continues to be the second leading cause of cancer mortality in women a consequence of recurrence and metastasis. In recent years, a population of cancer cells has been identified, called cancer stem cells (CSCs) with self-renewal capacity, proposed to underlie tumor recurrence and metastasis. We previously showed that the adipose tissue cytokine LEPTIN, increased in obesity, promotes the survival of CSCs in vivo. Here, we tested the hypothesis that the Leptin Receptor (LEPR), expressed in mammary cancer cells, is necessary for maintaining CSC-like and metastatic properties. We silenced LEPR via shRNA lentivirus transduction and determined that expression of stem cell self-renewal transcription factors NANOG, SOX2, and OCT4 are inhibited. LEPR-NANOG signaling pathway is conserved between species because we can rescue NANOG expression in human LEPR-silenced cells with the mouse LepR. Using a NANOG promoter GFP reporter, we showed that LEPR is enriched in NANOG promoter active (GFP+) cells. Using lineage tracing, we showed that the GFP+ cells exhibit symmetric and asymmetric division and cell death. LEPR silenced MDA-MB-231 cells exhibit a mesenchymal to epithelial transition morphologically, increased E-CADHERIN and decreased VIMENTIN expression compared to control cells. Finally, LEPR silenced cells exhibit reduced cell proliferation, self-renewal in tumorsphere assays, and tumor outgrowth in xenotransplant studies. Given the emergence of NANOG as a pro-carcinogenic protein in multiple cancers, these studies suggest that inhibition of LEPR may be a promising therapeutic approach to inhibit NANOG and thereby neutralize CSC functions.

The treatment for relapsed/refractory multiple myeloma (RRMM) continues to be challenging despite recent therapeutic advancements. Venetoclax, an inhibitor of the anti-apoptotic protein BCL-2, is a promising agent, especially in patients harbouring t(11;14). Our objective was to review our experience with venetoclax-based regimens at our institution. All ten RRMM patients treated with venetoclax were included and had a median of six prior lines of therapy. The overall response rate was 78% and one patient with cardiac amyloidosis and MM achieved a cardiac organ response. Haematologic toxicities requiring red blood cell and platelet transfusion and non-haematologic toxicities, most commonly gastrointestinal upset, were observed.

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Background: Light Chain (AL) amyloidosis is the most common form of systemic amyloidosis and refers to the deposition of abnormally folded monoclonal light chains or their fragments which can cause organ dysfunction. While treatment with autologous stem cell transplantation needs to be considered in patients who qualify, the increased use of proteasome inhibitors in the past decade has led to deeper hematologic and organ responses. Daratumumab, a CD-38 monoclonal antibody, has also showed promising therapeutic benefit. Given the major advances in AL amyloidosis, our objective was to evaluate presentations, management, and outcomes in AL amyloidosis patients diagnosed from January 2012-April 2020 at our institution. Methods: The Cleveland Clinic electronic medical record was queried to identify patients with a confirmed diagnosis of AL amyloidosis from January 2012 until April 2020. All patients over the age of 18 who followed up at the Cleveland Clinic after their initial diagnosis were included. Of 255 patients that were initially queried, 161 were ultimately able to be evaluated and met inclusion criteria. Clinical data was reviewed by authors D.B. and J.T. and conflicts were resolved by consensus. The primary endpoint was overall survival (OS). Results: A total of one hundred sixty-one patients were evaluated with baseline characteristics in Table 1. Among them, 92 (57.14%) were males, 69 (42.86%) were females, 92 (57.14%) had cardiac involvement at diagnosis, and 86 (53.42%) had kidney involvement at diagnosis. Also, 61 patients (37.89%) had a Revised Mayo stage of 3 or 4 at diagnosis. Thirty-nine patients (24.22%) underwent autologous stem cell transplantation as part of their treatment regimen. The two-year overall survival (OS) rate was 0.71 (95%CI: 0.64-.79), five-year OS rate was 0.60 (95%CI:0.52-0.69), and the median OS was not reached in this cohort of patients (Table 2). OS was also evaluated by patient group (Table 2). Conclusion: Given the recent major advancements in the treatment of AL amyloidosis, we evaluated the presentation, treatment, and outcomes in 161 patients with a diagnosis of AL amyloidosis at the Cleveland Clinic from January 2012-April 2020. A wide variety of patients with AL amyloidosis were evaluated and overall survival by patient group showed significantly better OS in patients age <65 at diagnosis, patients without cardiac involvement, and patients with Revised Mayo stage 2 or less at diagnosis, with a five-year overall response rate of 0.60(95%CI:0.52-0.69) for all patients. Our patient experience highlights the efficacy of proteasome inhibitor use in the past decade for the treatment of AL amyloidosis and also reflect the use of newer agents such as daratumumab. While many major milestones have been achieved in the treatment of AL amyloidosis, more data is needed to assess the optimal duration and appropriate setting for newer therapeutics for this formidable disease. Disclosures Valent: Takeda Pharmaceuticals: Other: Teaching, Speakers Bureau; Amgen Inc.: Other: Teaching, Speakers Bureau; Celgene: Other: Teaching, Speakers Bureau.

Background: Delays in cancer care can have a detrimental impact on breast cancer outcomes. Despite advances in breast cancer treatment and improvements in survival, disparities between racial groups persist. At our own institution, we observed worse breast cancer outcomes in Black versus White patients in spite of similar treatments received. Higher stage at diagnosis and differences in histology appeared to account for only part of the difference. In this study, we evaluate the impact of race on time to initiation of first oncology treatment and overall survival in a large cohort of breast cancer patients treated at our center. Methods: Women diagnosed with stage I-IV breast cancer between 2015 and 2020 at the Cleveland Clinic were identified from our local tumor registry. All women over the age of 18 who followed up at the Cleveland Clinic Main Campus and identified as either Black or White in the electronic medical record (EMR) were included in the initial query. Men and individuals who identified as a race other than Black or White were excluded due to small numbers. There were forty-nine patients in whom the date of first treatment was unknown. Clinical data were reviewed by author D.B. and data not available in the tumor registry were obtained from the EMR. Baseline characteristics, and time to first treatment initiation were reported. Time to treatment initiation was defined as the days from biopsy demonstrating cancer to the date of initiation of any breast cancer treatment modality (surgery, chemotherapy, endocrine therapy, or radiation therapy). Results: A total of 6095 patients were included in the analysis with a median follow-up of 2.7 years. Median age was 62 and Black patients were slightly older than White patients (63 years [range 21-98] versus 62 [range 21-99]; p=0.048). Fewer Black patients had private insurance (38% versus 51%) and more had Medicaid or Medicare compared to White patients (59% versus 45%) (p<0.001). Only 1% of patients had no insurance and this was similar for both Black and White patients. The time from diagnosis to treatment differed by race. Black patients had a median of 36 days from diagnosis to treatment and White patients had a median of 32 days from diagnosis to treatment (p<0.001). Three-year overall survival was 86% (95% CI: 83-89%) for Black patients and 92% (95%CI: 91%-93%) for White patients (p<0.0001). No difference was observed in breast cancer recurrence rates by race (p=0.56). Additional analyses will investigate the contribution of comorbidities, cancer stage, histology, and other patient related factors to racial disparities in overall survival and time to treatment. Conclusion:. Our study highlights real world data on racial disparities in breast cancer treatment initiation and overall survival. Further investigation will seek to identify the impact of patient related factors on these important outcomes. It is critically important for breast cancer treatment teams to be aware of these racial disparities to implement interventions that can attempt to limit them. Citation Format: Diana Basali, Emily C. Zabor, Narcissa Houston, Halle CF Moore. Impact of race on time to treatment initiation and survival in breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-14-13.