Zari DS, Novak R, Haviv O, Ron I, Kaplan B, Awad B, Norman D, Nikomarov D. Anatomical distribution of bone metastases in stage IV breast cancer: According to histological subtype. World J Clin Oncol 2025; 16(9): 110087 [PMID: 41024829 DOI: 10.5306/wjco.v16.i9.110087]
Corresponding Author of This Article
David Shaked Zari, MD, Department of Orthopedic Surgery, Rambam Medical Center, Hallya Hashniya, Haifa 3501115, Israel. shaked.zaki1009@gmail.com
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Orthopedics
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Retrospective Cohort Study
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Sep 24, 2025 (publication date) through Feb 23, 2026
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World Journal of Clinical Oncology
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2218-4333
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Zari DS, Novak R, Haviv O, Ron I, Kaplan B, Awad B, Norman D, Nikomarov D. Anatomical distribution of bone metastases in stage IV breast cancer: According to histological subtype. World J Clin Oncol 2025; 16(9): 110087 [PMID: 41024829 DOI: 10.5306/wjco.v16.i9.110087]
World J Clin Oncol. Sep 24, 2025; 16(9): 110087 Published online Sep 24, 2025. doi: 10.5306/wjco.v16.i9.110087
Anatomical distribution of bone metastases in stage IV breast cancer: According to histological subtype
David Shaked Zari, Rostislav Novak, Or Haviv, Itay Ron, Ben Kaplan, Bana Awad, Doron Norman, David Nikomarov
David Shaked Zari, Rostislav Novak, Or Haviv, Itay Ron, Ben Kaplan, Bana Awad, Doron Norman, David Nikomarov, Department of Orthopedic Surgery, Rambam Medical Center, Haifa 3501115, Israel
David Shaked Zari, Rostislav Novak, Or Haviv, Itay Ron, Ben Kaplan, Bana Awad, Doron Norman, David Nikomarov, Technion Israel Institute of Technology, The Ruth and Bruce Rappaport Faculty of Medicine, Haifa 3501115, Israel
Author contributions: Zari DS designed the research, curated the data, performed formal analysis, and wrote the original draft; Novak R performed the investigation, curated the data, and contributed to writing; Haviv O developed the software, performed validation and visualization, and contributed to writing and editing; Ron I contributed to methodology, project administration, and statistical analysis; Kaplan B curated the data, performed investigation, and contributed to writing and editing; Awad B collected the data, performed formal analysis, and contributed to writing and editing; Norman D contributed to methodology and provided supervision; Nikomarov D performed statistical analysis, validation, supervision, and contributed to writing.
Institutional review board statement: This retrospective cohort study was approved by the Rambam Medical Center’s Institutional Review Board (IRB ID: RMB-0110-22) and was conducted in accordance with the Declaration of Helsinki.
Informed consent statement: Due to the retrospective nature of the study and the use of anonymized data, the ethics committee waived the requirement for informed consent from patients.
Conflict-of-interest statement: The authors declare that they have no conflict of interest related to the publication of this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: This manuscript is original, has not been published, and is not under consideration elsewhere.
Corresponding author: David Shaked Zari, MD, Department of Orthopedic Surgery, Rambam Medical Center, Hallya Hashniya, Haifa 3501115, Israel. shaked.zaki1009@gmail.com
Received: May 29, 2025 Revised: June 24, 2025 Accepted: August 5, 2025 Published online: September 24, 2025 Processing time: 117 Days and 17.6 Hours
Abstract
BACKGROUND
Bone is the most common site of metastasis in breast cancer, yet limited data exist regarding the precise anatomical distribution of bone metastases by tumor subtype.
AIM
To examine the anatomical distribution of the first bone metastases in stage IV breast cancer, stratified by histological subtype. Secondary objectives include analyzing the anatomical distribution of subsequent bone metastases, Metastasis-Free Survival (MFI), Progression-Free Interval (PFI), and overall survival (OS).
METHODS
A retrospective cohort study was conducted on 107 adult females with stage IV breast cancer and bone metastases between 2013 and 2023. Patients were classified by histological subtype (Luminal A/B, HER2-enriched, and Triple-Negative). First and subsequent bone metastasis locations were identified via computed tomography, positron emission tomography/CT, or magnetic resonance imaging. Survival analyses included MFI, PFI, and OS.
RESULTS
Rib metastases were significantly more common in HER2-enriched tumors (80%, P = 0.041), while scapula/clavicle metastases were more prevalent in Triple-Negative cases (37.5%, P = 0.003). Subsequent bone metastases mirrored initial patterns, with pelvic involvement notably higher in HER2-enriched (60%) and luminal B (58%) patients (P = 0.046). No significant differences were found in MFI, PFI, or OS among subtypes. Receptor-based analysis showed no significant variation in bone metastasis locations.
CONCLUSION
Breast cancer subtypes are associated with suggestive bone metastasis patterns—specifically, rib involvement in HER2-enriched and scapula/clavicle in Triple-Negative cases. While anatomical variations exist, they did not translate into differential survival or fracture risk in this cohort.
Core Tip: This study investigates the anatomical distribution of bone metastases in stage IV breast cancer, stratified by histological subtype. Unlike previous reports focusing on general metastatic trends, our analysis highlights specific skeletal predilections-such as rib involvement in HER2-enriched tumors and scapula/clavicle in triple-negative cases. Despite these patterns, survival outcomes and fracture rates did not significantly differ. These findings support a unified clinical approach while offering new insights that may refine imaging surveillance strategies.
