{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:02:43Z","timestamp":1790791363798,"version":"4.1.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bone metastases (BM) are still the main cause of morbidity in cancer patients because of skeletal-related events (SREs) that reduce quality of life. They have also led to increased social and healthcare costs. At present, data available on BM are insufficient. This was a multicentre prospective observational study of patients with BM from breast cancer (BC) with at least 6\u00a0months\u2019 follow-up. Information on patients at the first diagnosis of BM, including demographics and characteristics of the primary tumor and BM. Data were periodically updated by participating centres and reviewed by the coordinator centre. From October 2014 to July 2019, 618 patients with BM from solid tumors were enrolled and 220 were eligible for the present study. Median age was 62\u00a0years (range 26\u201386). Median follow-up was 34\u00a0months (range 6\u2013149). At the time of enrolment, 109 (50%) had only BM (BOM) and 109 (50%) had concomitant visceral lesions and BM (BVM). Median time-to-first BM was 47\u00a0months (range 0\u2013312) in BOM and 78.6\u00a0months in BVM patients. Disease-free interval differed on the basis of BC molecular subtype and stage. Ninety-eight BM patients had at least on SRE. Zoledronate was used in 69.1% of cases and denosumab in 28.3%. First-line treatment was hormone-based (50.7%), chemotherapy-based (38.7%) or chemotherapy-\u2009+\u2009hormone therapy-based (9.7%). Median progression-free and overall survival were 15.1\u00a0months (95% CI 12.6\u201318.4) and 66.8\u00a0months (95% CI 52.1\u201379.2), respectively. Our prospective study could substantially help to better understand the natural history of BM from BC.<\/jats:p>","DOI":"10.1038\/s41598-021-83749-1","type":"journal-article","created":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T11:06:57Z","timestamp":1613992017000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["First prospective data on breast cancer patients from the multicentre italian bone metastasis database"],"prefix":"10.1038","volume":"11","author":[{"given":"Alberto","family":"Bongiovanni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Foca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Fantini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rosachiara","family":"Forcignan\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Artioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossana","family":"Berardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Campadelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Procopio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Silvestris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada","family":"Riva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Gurrieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Angela","family":"Debonis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giandomenico","family":"Di Menna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Fausti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Recine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Vespignani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,22]]},"reference":[{"issue":"20","key":"83749_CR1","doi-asserted-by":"publisher","first-page":"3271","DOI":"10.1200\/JCO.2009.25.9820","volume":"28","author":"H Kennecke","year":"2010","unstructured":"Kennecke, H. et al. Metastatic behavior of breast cancer subtypes. J. Clin. Oncol. 28(20), 3271\u20133277 (2010).","journal-title":"J. Clin. Oncol."},{"issue":"1","key":"83749_CR2","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/bjc.1987.13","volume":"55","author":"R Coleman","year":"1987","unstructured":"Coleman, R. & Rubens, R. The clinical course of bone metastases from breast cancer. Br. J. Cancer 55(1), 61\u201366 (1987).","journal-title":"Br. J. Cancer"},{"issue":"8","key":"83749_CR3","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1038\/nrc867","volume":"2","author":"GR Mundy","year":"2002","unstructured":"Mundy, G. R. Metastasis to bone: Causes, consequences and therapeutic opportunities. Nat. Rev. Cancer 2(8), 284\u2013293 (2002).","journal-title":"Nat. Rev. Cancer"},{"issue":"3","key":"83749_CR4","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1053\/ctrv.2000.0210","volume":"27","author":"RE Coleman","year":"2001","unstructured":"Coleman, R. E. Metastatic bone disease: Clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 27(3), 165\u2013176 (2001).","journal-title":"Cancer Treat Rev."},{"issue":"1","key":"83749_CR5","first-page":"321","volume":"11","author":"F Macedo","year":"2017","unstructured":"Macedo, F. et al. Bone metastases: An overview. Oncol. Rev. 11(1), 321 (2017).","journal-title":"Oncol. Rev."},{"key":"83749_CR6","doi-asserted-by":"publisher","first-page":"306","DOI":"10.3892\/ol.2013.1372","volume":"2","author":"T Ibrahim","year":"2013","unstructured":"Ibrahim, T., Mercatali, L. & Amadori, D. A new emergency in oncology: Bone metastases in breast cancer patients (Review). Oncol. Lett. 2, 306\u2013310 (2013).","journal-title":"Oncol. Lett."},{"issue":"2","key":"83749_CR7","first-page":"121","volume":"10","author":"T Ibrahim","year":"2013","unstructured":"Ibrahim, T., Mercatali, L. & Amadori, D. Bone and cancer: the osteoncology. Clin. Cases Miner. Bone Metab. 10(2), 121\u2013123 (2013).","journal-title":"Clin. Cases Miner. Bone Metab."},{"issue":"2","key":"83749_CR8","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1097\/01.mlr.0000108746.69256.45","volume":"42","author":"KP Weinfurt","year":"2004","unstructured":"Weinfurt, K. P. et al. Health related quality of life among patients with breast cancer receiving zoledronic acid or pamidronate disodium for metastatic bone lesions. Med. Care 42(2), 164\u2013175 (2004).","journal-title":"Med. Care"},{"issue":"20 Pt 2","key":"83749_CR9","doi-asserted-by":"publisher","first-page":"6243s","DOI":"10.1158\/1078-0432.CCR-06-0931","volume":"12","author":"RE Coleman","year":"2006","unstructured":"Coleman, R. E. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin. Cancer Res. 12(20 Pt 2), 6243s-s6249 (2006).","journal-title":"Clin. Cancer Res."},{"issue":"4","key":"83749_CR10","doi-asserted-by":"publisher","first-page":"e007702","DOI":"10.1136\/bmjopen-2015-007702","volume":"5","author":"K Cetin","year":"2015","unstructured":"Cetin, K. et al. Survival in patients with breast cancer with bone metastasis: A Danish population-based cohort study on the prognostic impact of initial stage of disease at breast cancer diagnosis and length of the bone metastasis-free interval. BMJ Open 5(4), e007702 (2015).","journal-title":"BMJ Open"},{"issue":"12","key":"83749_CR11","doi-asserted-by":"publisher","first-page":"3279","DOI":"10.1007\/s00520-013-1887-3","volume":"21","author":"G Oster","year":"2013","unstructured":"Oster, G. et al. Natural history of skeletal-related events in patients with breast, lung, or prostate cancer and metastases to bone: A 15-year study in two large US health systems. Support Care Cancer 21(12), 3279\u20133286 (2013).","journal-title":"Support Care Cancer"},{"issue":"5\u20136","key":"83749_CR12","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1159\/000107772","volume":"71","author":"ME Cazzaniga","year":"2006","unstructured":"Cazzaniga, M. E. et al. Diagnosis, management and clinical outcome of bone metastases in breast cancer patients: Results from a prospective, multicenter study. Oncology 71(5\u20136), 374\u2013381 (2006).","journal-title":"Oncology"},{"key":"83749_CR13","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.ejca.2017.03.031","volume":"79","author":"J Schr\u00f6der","year":"2017","unstructured":"Schr\u00f6der, J. et al. Treatment and pattern of bone metastases in 1094 patients with advanced breast cancer: Results from the prospective German Tumour Registry Breast Cancer cohort study. Eur. J. Cancer 79, 139\u2013148 (2017).","journal-title":"Eur. J. Cancer"},{"issue":"9","key":"83749_CR14","doi-asserted-by":"publisher","first-page":"3395","DOI":"10.1007\/s00520-019-4635-5","volume":"27","author":"A Bongiovanni","year":"2019","unstructured":"Bongiovanni, A. et al. Ten-year experience of the multidisciplinary osteoncology center. Support Care Cancer 27(9), 3395\u20133402 (2019).","journal-title":"Support Care Cancer"},{"issue":"3","key":"83749_CR15","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1023\/A:1006308619659","volume":"59","author":"EF Solomayer","year":"2000","unstructured":"Solomayer, E. F. et al. Metastatic breast cancer: Clinical course, prognosis and therapy related to the first site of metastasis. Breast Cancer Res. Treat 59(3), 271\u2013278 (2000).","journal-title":"Breast Cancer Res. Treat"},{"issue":"5","key":"83749_CR16","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1002\/pds.1200","volume":"15","author":"S Schneeweiss","year":"2006","unstructured":"Schneeweiss, S. Sensitivity analysis and external adjustment for unmeasured confounders in epidemiologic database studies of therapeutics. Pharmacoepidemiol. Drug Saf. 15(5), 291\u2013303 (2006).","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"83749_CR17","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/978-1-4614-5662-9_4","volume-title":"Metastatic Bone Disease: An Integrated Approach to Patient Care","author":"S Colonna","year":"2016","unstructured":"Colonna, S. & Werner, T. L. Breast cancer bone metastases. In Metastatic Bone Disease: An Integrated Approach to Patient Care (ed. Randall, R. L.) 45\u201355 (Springer, New York, 2016)."},{"key":"83749_CR18","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jbo.2018.01.004","volume":"11","author":"H Zhang","year":"2018","unstructured":"Zhang, H. et al. Incidence, risk factors and prognostic characteristics of bone metastases and skeletal-related events (SREs) in breast cancer patients: A systematic review of the real world data. J. Bone Oncol. 11, 38\u201350 (2018).","journal-title":"J. Bone Oncol."},{"issue":"2","key":"83749_CR19","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1634\/theoncologist.2010-0350","volume":"16","author":"N Niikura","year":"2011","unstructured":"Niikura, N. et al. Treatment outcome and prognostic factors for patients with bone-only metastases of breast cancer: A single-institution retrospective analysis. Oncologist 16(2), 155\u2013164 (2011).","journal-title":"Oncologist"},{"issue":"5","key":"83749_CR20","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.3349\/ymj.2013.54.5.1168","volume":"54","author":"SG Ahn","year":"2013","unstructured":"Ahn, S. G. et al. Prognostic factors for patients with bone-only metastasis in breast cancer. Yonsei Med. J. 54(5), 1168\u20131177 (2013).","journal-title":"Yonsei Med. J."},{"issue":"2","key":"83749_CR21","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1007\/s10549-011-1594-z","volume":"130","author":"T Foukakis","year":"2011","unstructured":"Foukakis, T. et al. Age-specific trends of survival in metastatic breast cancer: 26 years of longitudinal data from a population-based cancer registry in Stockholm, Sweden. Breast Cancer Res. Treat 130(2), 553\u2013560 (2011).","journal-title":"Breast Cancer Res. Treat"},{"issue":"11","key":"83749_CR22","doi-asserted-by":"publisher","first-page":"2586","DOI":"10.1002\/cam4.1224","volume":"6","author":"S Li","year":"2017","unstructured":"Li, S. et al. Development and validation of a nomogram predicting the overall survival of stage IV breast cancer patients. Cancer Med. 6(11), 2586\u20132594 (2017).","journal-title":"Cancer Med."},{"issue":"7","key":"83749_CR23","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1002\/1097-0142(19901001)66:7<1621::AID-CNCR2820660729>3.0.CO;2-G","volume":"66","author":"G Falkson","year":"1990","unstructured":"Falkson, G. et al. Survival of premenopausal women with metastatic breast cancer. Long-term follow-up of Eastern Cooperative Group and Leukemia Group B studies. Cancer 66(7), 1621\u20139 (1990).","journal-title":"Cancer"},{"key":"83749_CR24","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1186\/1477-7819-12-344","volume":"12","author":"K Kontani","year":"2014","unstructured":"Kontani, K. et al. Factors responsible for long-term survival in metastatic breast cancer. World J. Surg. Oncol. 12, 344 (2014).","journal-title":"World J. Surg. Oncol."},{"issue":"10","key":"83749_CR25","first-page":"5637","volume":"34","author":"W Rhomberg","year":"2014","unstructured":"Rhomberg, W. & Rhomberg, T. Long-term survival in patients with incurable breast cancer. Anticancer Res. 34(10), 5637\u20135642 (2014).","journal-title":"Anticancer Res."},{"issue":"2","key":"83749_CR26","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1038\/bjc.1998.52","volume":"77","author":"RE Coleman","year":"1998","unstructured":"Coleman, R. E., Smith, P. & Rubens, R. D. Clinical course and prognostic factors following bone recurrence from breast cancer. Br. J. Cancer 77(2), 336\u2013340 (1998).","journal-title":"Br. J. Cancer"},{"issue":"11","key":"83749_CR27","first-page":"904","volume":"49","author":"B Kuru","year":"2008","unstructured":"Kuru, B. et al. Prognostic factors for survival in breast cancer patients who developed distant metastasis subsequent to definitive surgery. Singapore Med. J. 49(11), 904\u2013911 (2008).","journal-title":"Singapore Med. J."},{"key":"83749_CR28","doi-asserted-by":"publisher","first-page":"101","DOI":"10.2147\/CLEP.S5446","volume":"1","author":"A\u00d8 Jensen","year":"2009","unstructured":"Jensen, A. \u00d8. et al. Validity of the recorded International Classification of Diseases, 10th edition diagnoses codes of bone metastases and skeletal-related events in breast and prostate cancer patients in the Danish National Registry of Patients. Clin. Epidemiol. 1, 101\u2013108 (2009).","journal-title":"Clin. Epidemiol."},{"issue":"1","key":"83749_CR29","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.clbc.2013.09.003","volume":"14","author":"LS Schwartzberg","year":"2014","unstructured":"Schwartzberg, L. S. et al. Phase II trial of fulvestrant with metronomic capecitabine for postmenopausal women with hormone receptor-positive, HER2\u2212negative metastatic breast cancer. Clin. Breast Cancer 14(1), 13\u201319 (2014).","journal-title":"Clin. Breast Cancer"},{"issue":"2","key":"83749_CR30","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.canlet.2014.01.008","volume":"346","author":"D Jiang","year":"2014","unstructured":"Jiang, D. et al. Fulvestrant, a selective estrogen receptor down-regulator, sensitises estrogen receptor negative breast tumours to chemotherapy. Cancer Lett. 346(2), 292\u2013299 (2014).","journal-title":"Cancer Lett."},{"issue":"11","key":"83749_CR31","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1634\/theoncologist.2018-0085","volume":"23","author":"A Parkes","year":"2018","unstructured":"Parkes, A. et al. Prognostic factors in patients with metastatic breast cancer with bone-only metastases. Oncologist 23(11), 1282\u20131288 (2018).","journal-title":"Oncologist"},{"issue":"2","key":"83749_CR32","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1007\/s10549-017-4510-3","volume":"167","author":"D Cronin-Fenton","year":"2018","unstructured":"Cronin-Fenton, D. et al. Breast cancer recurrence, bone metastases, and visceral metastases in women with stage II and III breast cancer in Denmark. Breast Cancer Res. Treat 167(2), 517\u2013528 (2018).","journal-title":"Breast Cancer Res. Treat"},{"key":"83749_CR33","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.ejca.2017.12.012","volume":"91","author":"NM deSouza","year":"2018","unstructured":"deSouza, N. M. et al. Strategies and technical challenges for imaging oligometastatic disease: Recommendations from the European Organisation for Research and Treatment of Cancer imaging group. Eur. J. Cancer 91, 153\u2013163 (2018).","journal-title":"Eur. J. Cancer"},{"key":"83749_CR34","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.radonc.2018.11.022","volume":"131","author":"MT Milano","year":"2019","unstructured":"Milano, M. T. et al. Oligometastatic breast cancer treated with hypofractionated stereotactic radiotherapy: Some patients survive longer than a decade. Radiother. Oncol. 131, 45\u201351 (2019).","journal-title":"Radiother. Oncol."},{"issue":"3","key":"83749_CR35","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1159\/000345795","volume":"84","author":"T Ibrahim","year":"2013","unstructured":"Ibrahim, T. et al. Hormonal receptor, human epidermal growth factor receptor-2, and Ki67 discordance between primary breast cancer and paired metastases: clinical impact. Oncology 84(3), 150\u2013157 (2013).","journal-title":"Oncology"},{"issue":"9","key":"83749_CR36","doi-asserted-by":"publisher","first-page":"849","DOI":"10.2217\/fon-2017-0384","volume":"14","author":"E Ongaro","year":"2018","unstructured":"Ongaro, E. et al. Comparison of primary breast cancer and paired metastases: Biomarkers discordance influence on outcome and therapy. Future Oncol. 14(9), 849\u2013859 (2018).","journal-title":"Future Oncol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-83749-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-83749-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-83749-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T03:58:53Z","timestamp":1670039933000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-83749-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,22]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["83749"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-83749-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,22]]},"assertion":[{"value":"14 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 February 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4329"}}