Koizumi et al. BMC Cancer 2010, 10:423 http://www.biomedcentral.com/1471-2407/10/423 R E S E A R C H A R T I C L E Open Access Post-operative breast cancer patients diagnosed with skeletal metastasis without bone pain had fewer skeletal-related events and deaths than those with bone pain Mitsuru Koizumi1,2*, Masataka Yoshimoto3,5, Fujio Kasumi3,6, Takuji Iwase3, Etsuro Ogata4 Abstract Background: Skeletal metastases are often accompanied by bone pain. To investigate the clinical meaning of bone pain associated with skeletal metastasis in breast cancer patients after surgery, we explored whether the presence of bone pain was due to skeletal-related events (SREs) or survival (cause specific death, CSD), retrospectively. Methods: Consecutive breast cancer patients undergoing surgery between 1988 and 1998 were examined for signs of skeletal metastasis until December 2006. Patients who were diagnosed as having skeletal metastasis were the subjects of this study. Bone scans were performed annually for 5, 7 or 10 years; they were also conducted if skeletal metastasis was suspected. Data concerning bone pain and tumor markers at the time of skeletal metastasis diagnosis, and data relating to various factors including tumors, lymph nodes and hormone receptors at the time of surgery, were investigated. The relationships between factors such as bone pain, SRE and CSD were analyzed using the Kaplan-Meier method and Cox’s analysis. Results: Skeletal metastasis occurred in 668 patients but the pain status of two patients was unknown, therefore 666 patients were included in the study. At the time of skeletal metastasis diagnosis 270 patients complained of pain; however, 396 patients did not. Analysis of data using Cox’s and Kaplan-Meier methods demonstrated that patients without pain had fewer SREs and better survival rates than those with pain. Hazard ratios regarding SRE (base = patients without pain) were 2.331 in univariate analysis and 2.243 in multivariate analysis. Hazard ratios regarding CSD (base = patients without pain) were 1.441 in univariate analysis and 1.535 in multivariate analysis. Similar results were obtained when analyses were carried out using the date of surgery as the starting point. Conclusion: Bone pain at diagnosis of skeletal metastasis was an indicator of increased SRE and CSD. However, these data did not support recommendations of follow-up bone surveys in breast cancer patients. Background Skeletal metastasis is a common complication of breast cancer; more than 70% of patients who die from breast cancer exhibit osseous metastasis at autopsy [1]. How- ever, the high incidence of metastasis at autopsy is not considered sufficient evidence to perform routine bone surveys on breast cancer patients [2]. The reason given * Correspondence: mitsuru@nirs.go.jp 1Molecular Imaging Center, National Institutes of Radiological Sciences, Anagawa 4-9-1, Inage-ku, Chiba, 263-8555 Japan Full list of author information is available at the end of the article is that there is no evidence that such surveys would improve patients’ survival and quality of life [3-5]. There have been significant advancements in hormone therapy and chemotherapy for advanced breast cancer sufferers [6-8]. Furthermore, use of bisphosphonates to treat skeletal metastasis associated with breast cancer has been developed. Bisphosphonates reduce skeletal- related events (SREs) in patients with skeletal metastasis [9-13]. An analysis of the first appearance of skeletal metastasis in breast cancer patients revealed that patients with a solitary metastasis to bone (solitary bone © 2010 Koizumi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.