Lathrop, Kate

Abstract Background: Recent advancements in novel therapeutics have resulted in improved survival over the last decade for patients with metastatic breast cancer, but there remain subsets of patients who experience disproportionately poor outcomes. Patients with visceral crisis (VC), defined by the 5th ESO ESMO as the presence of visceral metastasis with severe organ compromise and/or rapid progression, are often excluded from clinical trials of novel therapeutics. This is despite patients with VC having poorer clinical outcomes and a lack of guidelines consensus on best therapeutic practices. Thus, we sought to better characterize this patient cohort via a meta-analysis to elucidate clinical characteristics and treatment options. Methods: We searched MEDLINE, Embase, Cochrane, Scopus and other sources, from each database's inception to March 2023. The search strategy was designed and conducted by an experienced librarian with input from the study's principal investigator. Controlled vocabulary supplemented with keywords was used to search for patients with breast cancer in visceral crisis. Outcomes of interest included mortality and progression at different time points. Meta-analysis was conducted using the random-effects model. Results: The studies matching our initial inquiry was 154. After evaluation for patient number, and VC related outcomes, 16 studies (12 abstract only) met initial criteria. After data extraction, 12 studies were excluded due to insufficient outcomes delineated by VC. The treatment period was 01/2008 until 01/2022. The mean age at diagnosis of VC was 53.9 with a total of 6404 patients, 6259 were hormone positive, 41 Her2 positive and 87 triple negative. The type of VC included 212 liver dysfunction, 84 respiratory dysfunction, 40 with bone marrow dysfunction, 4 with SVC syndrome, and 43 with meningeal disease (VC type is not reported in every study). The treatments were varied and included multiple platinum doublets, CDK4/6 with endocrine therapy, platinum with bevacizumab, endocrine monotherapy and Her-2 targeted agents. Unfortunately, the number of patients per treatment group or VC type is not enough for targeted outcome analysis. The proportion of patients who progressed at 1, 6, 12 and 18 months were 0.17, 0.64, 0.95 and 0.91 respectively (2 studies Yang et al and Funasaka et al). Mortality assessed as proportion who expired at 1, 6, 12 and 18 months at 0.07, 0.44, 0.64 and 0.77 respectively (3 studies Yang et al, Funasaka et al and Franzoi et al) and at 24 months 0.89 in 4 studies (Yang et al, Funasaka et al, Dawood et al and Franzoi et al) (Table 1). Conclusions In this systematic review, we clearly demonstrate a lack of clinical trial data available to demonstrate specific outcomes based on chemotherapy, visceral crisis type or targeted treatment. The prognosis, however, is consistently poor with mortality at 64 percent by 12 months. Thus, further studies are needed to guide best treatment strategies that address both the poor clinical outcomes and therapeutic toxicities for patients with VC. Clinical trial groups and regulatory bodies overseeing new drug development for breast cancer should consider specific arms for patients with VC, instead of targeted exclusion from trials, as this strategy has proven effective in expansion of therapeutics for other challenging breast cancer subtypes. Table 1 Table 1: Proportion of progression and mortality. Progression studies include Yang et al 2022, Funasaka et al 2021. Mortality studies at 1, 6 and 12 months Yang et al 2022, Funasaka et al 2021 and Franzoi et al 2021. Mortality studies at 24 months Yang et al 2022, Funasaka et al 2021, Franzoi et al 2021, Dawood et al 2021. Citation Format: Michael Auster, Raed Benkhadra, Sophia Lee, Tamarah Aldawoodi, Larry Prokop, Tarek Nayfeh, Paromita Datta, Kate Lathrop. Meta-Analysis of Clinical Characteristics and Outcomes in Breast Cancer Patients with Visceral Crisis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-06-03.

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. Results: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32–1.67]); Black patients (aOR 1.74; 95 CI 1.24–2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70–6.79) and Other (aOR 2.97; 95 CI 1.71–5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83–12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63–3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20–2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66–3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89–22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients. Funding: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. Clinical trial number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701 .