Abstract P1-06-01: Insights from rapid autopsy shed light on mechanisms of cancer dissemination in metastatic breast cancer

Abstract

Previously we presented our initial findings from a 9-patient rapid autopsy pilot for metastatic breast cancer (MBC). At the time of procurement, one third of subjects exhibited clinically unidentified diseased sites in organs not commonly associated with breast cancer metastases, 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 a pathologist. We now expand upon these findings in a more in-depth exploration of the presence of micro-metastases in presumed tumor-negative tissues. A subset of tumor-free tissues were selected from each patient (average of 10 specimens per patient). All selected specimens were negative by clinical imaging, appeared grossly normal at procurement, and were reported to be tumor negative by H&E assessment by a clinical pathologist. We included organs both commonly and uncommonly involved in MBC, including lung, bone, spleen, pancreas, kidney, and non-tumor draining lymph nodes. Tissues were stained for one or more of the markers, pan-cytokeratin, GATA-3, HMFG, MUC1, and ER (if patient was previously ER+), depending on tissue type. Of the 87 total specimens assessed, we identified micro-metastases in 13 specimens from 4 individual patients. Across these 4 patients, micro-metastases were found in lung, bone, pancreas, spleen, and several non-tumor draining lymph nodes. While lung and bone are commonly involved in MBC and these results are not entirely surprising, pancreas and spleen involvement is extraordinarily rare. Further surprising was the identification of micro-metastases in several lymph nodes that were not located anatomically downstream from a disease-involved organ. Image patterns demonstrate tumor cell infiltration into the lymph node within the subcapsular sinus. Presence of micro-metastases in tumor-negative tissue did not correlate with tumor hormone status or cancer type (e.g. lobular vs DCIS). Combined with our previous findings, we now report unexpected and clinically undiagnosed disease involvement in 6/9, or two-thirds, of our patients. Based on these findings, we hypothesize that cancer stem cells and/or micro-metastases are present throughout the body, in all tissue types, and that their ability to grow into tumors is regulated by the local immune microenvironment. Lastly, the differing roles and mechanics of lymphatic vs hematological spread in metastatic disease has long been discussed. Our findings provide strong evidence for cancer dissemination through the lymphatics system. Further study is necessary to better understand the timing of metastatic spread, whether systemic dissemination occurs early or later in disease, and if conducive metastatic or pre-metastatic niches are already present throughout the body at the time of primary diagnosis or if these permissive environments develop slowly overtime. Citation Format: Eliza R. Bacon, Kena Ihle, Colt Egelston, Weihua Guo, Diana Simons, Dan Schmolze, Christina Wei, Lusine Tumyan, Peter P Lee, James R. Waisman. Insights from rapid autopsy shed light on mechanisms of cancer dissemination in metastatic breast cancer [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 P1-06-01.