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      Incidence of bone metastases and skeletal-related events in breast cancer patients: A population-based cohort study in Denmark

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          Abstract

          Background

          Breast cancer (BrCa) is the most commonly diagnosed cancer among women in the industrialized world. More than half of women presenting with metastatic BrCa develop bone metastases. Bone metastases increase the risk of skeletal-related events (SREs), defined as pathological fractures, spinal cord compression, bone pain requiring palliative radiotherapy, and orthopaedic surgery. Both bone metastases and SREs are associated with unfavorable prognosis and greatly affect quality of life. Few epidemiological data exist on SREs after primary diagnosis of BrCa and subsequent bone metastasis. We therefore estimated the incidence of bone metastases and SREs in newly-diagnosed BrCa patients in Denmark from 1999 through 2007.

          Methods

          We estimated the overall and annual incidence of bone metastases and SREs in newly-diagnosed breast cancer patients in Denmark from January 1, 1999 to December 31, 2007 using the Danish National Patient Registry (DNPR), which covers all Danish hospitals. We estimated the cumulative incidence of bone metastases and SREs and associated 95% confidence intervals (CI) using the Kaplan-Meier method.

          Results

          Of the 35,912 BrCa patients, 178 (0.5%) presented with bone metastases at the time of primary breast cancer diagnosis, and of these, 77 (43.2%) developed an SRE during follow up. A total of 1,272 of 35,690 (3.6%) BrCa patients without bone metastases at diagnosis developed bone metastases during a median follow-up time of 3.4 years. Among these patients, 590 (46.4%) subsequently developed an SRE during a median follow-up time of 0.7 years. Incidence rates of bone metastases were highest the first year after the primary BrCa diagnosis, particularly among patients with advanced BrCa at diagnosis. Similarly, incidence rates of a first SRE was highest the first year after first diagnosis of a bone metastasis.

          Conclusions

          The high incidence of SREs following the first year after first diagnosis of a bone metastasis underscores the need for early BrCa detection and research on effective treatments to delay the onset of SREs.

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          Most cited references11

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          Estimation of failure probabilities in the presence of competing risks: new representations of old estimators.

          A topic that has received attention in both the statistical and medical literature is the estimation of the probability of failure for endpoints that are subject to competing risks. Despite this, it is not uncommon to see the complement of the Kaplan-Meier estimate used in this setting and interpreted as the probability of failure. If one desires an estimate that can be interpreted in this way, however, the cumulative incidence estimate is the appropriate tool to use in such situations. We believe the more commonly seen representations of the Kaplan-Meier estimate and the cumulative incidence estimate do not lend themselves to easy explanation and understanding of this interpretation. We present, therefore, a representation of each estimate in a manner not ordinarily seen, each representation utilizing the concept of censored observations being 'redistributed to the right.' We feel these allow a more intuitive understanding of each estimate and therefore an appreciation of why the Kaplan-Meier method is inappropriate for estimation purposes in the presence of competing risks, while the cumulative incidence estimate is appropriate.
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            Epidemiology. When an entire country is a cohort.

            L. Frank (2000)
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              The clinical course of bone metastases from breast cancer.

              All patients with carcinoma of the breast seen in this Unit since 1970 were reviewed to study the incidence, prognosis, morbidity and response to treatment of bone metastases. The biological characteristics of the primary tumour were compared in patients relapsing first in bone or liver. Sixty-nine percent of patients dying with breast cancer had bone metastases and bone was the commonest site of first distant relapse. Bone relapse was more common in receptor positive or well differentiated (grade 1) tumours. The median survival was 24 months in those with disease apparently confined to the skeleton compared with 3 months after first relapse in liver. Ten percent of patients with breast cancer developed hypercalcaemia. All had metastatic disease and 85% had widespread skeletal involvement. Fifteen percent of patients with disease confined to the skeleton developed hypercalcaemia. The response in bone to primary endocrine therapy, and chemotherapy, was apparently less than the overall response achieved. A large proportion had apparently static disease reflecting the insensitivity of the UICC assessment criteria. The duration of survival in these patients was similar to responding patients, suggesting a tumour response may occur in the absence of discernable radiological evidence of healing.
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                Author and article information

                Journal
                BMC Cancer
                BMC Cancer
                BioMed Central
                1471-2407
                2011
                24 January 2011
                : 11
                : 29
                Affiliations
                [1 ]Department of Clinical Epidemiology, Aarhus University Hospital, Ole Worms Alle 1150, DK-8000 Århus C., Denmark
                [2 ]Center for Observational Research, Amgen Inc., One Amgen Center Drive, MS 24-2-A, Thousands Oaks CA 91320, USA
                Article
                1471-2407-11-29
                10.1186/1471-2407-11-29
                3037922
                21261987
                003bd162-1801-4d7c-b193-dee559414af7
                Copyright ©2011 Jensen 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.

                History
                : 23 July 2010
                : 24 January 2011
                Categories
                Research Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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