Needle biopsy accelerates pro-metastatic changes and systemic dissemination in breast cancer: Implications for mortality by surgery delay
Hiroyasu Kameyama, Priya Dondapati, R.M. Simmons, Macall Leslie, John F. Langenheim, Yunguang Sun, Misung Yi, Aubrey Rottschaefer, Rashmi Pathak, Shreya Nuguri, Kar‐Ming Fung, Shirng‐Wern Tsaih, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka
Abstract
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/PGE 2 /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.