%0 Journal Article
%T Needle biopsy accelerates pro-metastatic changes and systemic dissemination in breast cancer: Implications for mortality by surgery delay.
%A Kameyama H
%A Dondapati P
%A Simmons R
%A Leslie M
%A Langenheim JF
%A Sun Y
%A Yi M
%A Rottschaefer A
%A Pathak R
%A Nuguri S
%A Fung KM
%A Tsaih SW
%A Chervoneva I
%A Rui H
%A Tanaka T
%J Cell Rep Med
%V 4
%N 12
%D 2023 12 19
%M 38118415
%F 16.988
%R 10.1016/j.xcrm.2023.101330
%X Increased breast cancer (BC) mortality risk posed by delayed surgical resection of tumor after diagnosis is a growing concern, yet the underlying mechanisms remain unknown. Our cohort analyses of early-stage BC patients reveal the emergence of a significantly rising mortality risk when the biopsy-to-surgery interval was extended beyond 53 days. Additionally, histology of post-biopsy tumors shows prolonged retention of a metastasis-permissive wound stroma dominated by M2-like macrophages capable of promoting cancer cell epithelial-to-mesenchymal transition and angiogenesis. We show that needle biopsy promotes systemic dissemination of cancer cells through a mechanism of sustained activation of the COX-2/PGE2/EP2 feedforward loop, which favors M2 polarization and its associated pro-metastatic changes but are abrogated by oral treatment with COX-2 or EP2 inhibitors in estrogen-receptor-positive (ER+) syngeneic mouse tumor models. Therefore, we conclude that needle biopsy of ER+ BC provokes progressive pro-metastatic changes, which may explain the mortality risk posed by surgery delay after diagnosis.