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  3. Needle biopsy accelerates pro-metastatic changes and systemic dissemination in breast cancer: Implications for mortality by surgery delay

Needle biopsy accelerates pro-metastatic changes and systemic dissemination in breast cancer: Implications for mortality by surgery delay

  • Cell Rep Med. 2023 Dec 19;4(12):101330. doi: 10.1016/j.xcrm.2023.101330.
Hiroyasu Kameyama 1,  Priya Dondapati 1,  Reese Simmons 1,  Macall Leslie 1,  John F Langenheim 2,  Yunguang Sun 3,  Misung Yi 4,  Aubrey Rottschaefer 1,  Rashmi Pathak 1,  Shreya Nuguri 1,  Kar-Ming Fung 5,  Shirng-Wern Tsaih 6,  Inna Chervoneva 4,  Hallgeir Rui 2,  Takemi Tanaka 7
Affiliations

Affiliations

  • 1 Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE 10th St., Oklahoma City, OK 73104, USA.
  • 2 Department of Pharmacology, Physiology & Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, 233 S 10th St., BLSB 1008, Philadelphia, PA 19107, USA.
  • 3 Department of Pathology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
  • 4 Division of Biostatistics, Department of Pharmacology, Physiology & Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, 233 S 10th St., BLSB 1008, Philadelphia, PA 19107, USA.
  • 5 Department of Pathology, School of Medicine, University of Oklahoma Health Sciences Center, 940 Stanton L Young Boulevard, Oklahoma City, OK 73104, USA.
  • 6 Department of Obstetrics and Gynecology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
  • 7 Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE 10th St., Oklahoma City, OK 73104, USA; Department of Pathology, School of Medicine, University of Oklahoma Health Sciences Center, 940 Stanton L Young Boulevard, Oklahoma City, OK 73104, USA. Electronic address: takemi-tanaka@ouhsc.edu.
PMID: 38118415 DOI: 10.1016/j.xcrm.2023.101330
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/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.

Keywords

COX-2; EP2; M2 macrophage; breast cancer; epithelial-mesenchymal transition; metastasis; needle biopsy; prostaglandin E(2); surgery delay; wound healing.

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