Abstract PS19-16: Utility of rapid autopsy in cancer research: Unexpected findings and lessons learned from warm autopsies of metastatic breast cancer patients

Abstract

Metastatic disease is understudied largely because of inaccessibility to quality specimens for research use. The Legacy Project, a rapid or “warm”, autopsy program at City of Hope, seeks to overcome this challenge by collecting tissue from metastatic patients immediately (within 6 hours) after their death. This paradigm serves as a specimen resource to address many clinically relevant questions, such as disease heterogeneity and mechanisms driving disease progression. Using this model, we uncovered clinically relevant disease information that is normally unavailable while a subject is alive. In this study, 9 metastatic breast cancer patients and their families were approached and consented prior to death. The cohort includes a diversity of clinical presentations in terms of disease subtype, progression history, organ involvement, and final cause of death. A total of 533 specimens were collected across 9 subjects. The average time from death to specimen acquisition was 6.1 hours (range: 4.03 - 7.66 hours; median: 5.71 hours). Total number of specimens collected from each participant ranged from 38-75, with an average of 60 across all patients; the mean number of tumor-positive specimens collected was 29 (range 12-46); the mean number of non-cancer specimens collected was 31 (range 25-45). In patients with primary estrogen receptor (ER) positive disease, we observed variable heterogeneity in estrogen, progesterone, and ki67 status across metastatic lesions. Furthermore, we observed a profound shift in disease phenotype towards end of life, trending towards complete loss of hormone receptor expression and stark increase of Ki67 levels. At the time of procurement, one third of subjects exhibited clinically unidentified diseased sites in organs not commonly associated with breast cancer metastases a, including ovary, kidney, and pancreas. In two other instances, “resolved” bone specimens (as measured by absence of FTG uptake in PET/CT imaging) were later determined to be >30% tumor positive when assessed by H&E. While these preliminary findings generate more questions than answers regarding mechanisms of metastatic progression and resistance to therapy, they highlight the utility of rapid autopsy in a research setting. We suggest that many unanswered clinical questions can be addressed through interrogation of post-mortem tissues and we urge research institutions to thoughtfully consider adoption of the “rapid autopsy” model. Citation Format: Eliza R Bacon, Kena Ihle, Colt Egelston, Weihua Guo, Diana Simons, Peter P Lee, James Waisman. Utility of rapid autopsy in cancer research: Unexpected findings and lessons learned from warm autopsies of metastatic breast cancer patients [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 PS19-16.