Bisphosphonates in early breast cancer A systematic literature review November 2011 Funded by the National Breast Cancer Foundation Bisphosphonates in early breast cancer: a systematic literature review was prepared and produced by: Cancer Australia Locked Bag 3 Strawberry Hills NSW 2012 Australia Tel: +61 2 9357 9400 Fax: +61 2 9357 9477 Website: www.canceraustralia.gov.au © Cancer Australia 2011 ISBN Online: 978-1-74127-168-3 Recommended citation Cancer Australia. Bisphosphonates in early breast cancer: a systematic literature review. Cancer Australia, Surry Hills, NSW, 2011. Copyright statements: Paper-based publications This work is copyright. 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Contents Acknowledgements .................................................................................................................... iv Executive summary ..................................................................................................................... 1 1 Background ..................................................................................................................... 2 1.1 Breast cancer in Australia ..................................................................................... 2 1.2 Bisphosphonates in early breast cancer ............................................................... 2 1.3 Clinical practice guidelines .................................................................................... 2 2 Methods ........................................................................................................................... 4 2.1 Criteria for determining study eligibility ................................................................. 4 2.2 Literature search methodology ............................................................................. 4 2.3 Assessment of study eligibility .............................................................................. 5 2.4 Included studies .................................................................................................... 6 2.5 Conference abstracts ............................................................................................ 9 2.6 Appraisal of included studies .............................................................................. 12 2.7 Data analysis ...................................................................................................... 14 3 Description of included studies ................................................................................... 15 3.1 Systematic reviews ............................................................................................. 15 3.2 Primary studies ................................................................................................... 17 4 Results of included studies ......................................................................................... 32 4.1 Disease-free survival, recurrence-free survival, and survival without bone metastasis ....................................................................................................................... 32 4.2 Mortality and overall survival ............................................................................... 34 4.3 Adverse events ................................................................................................... 37 4.4 Cancer recurrence and metastasis ..................................................................... 43 4.5 Quality of life ....................................................................................................... 49 4.6 Spinal bone mineral density (BMD) .................................................................... 49 4.7 Bone mineral density (BMD) at locations other than the spine ........................... 57 4.8 Osteopenia/osteoporosis .................................................................................... 68 4.9 Fracture occurrence ............................................................................................ 74 5 Clinical practice guidelines .......................................................................................... 79 5.1 European Society for Medical Oncology (ESMO) 2010 ...................................... 79 5.2 New Zealand Ministry of Health 2009 ................................................................. 79 5.3 UK Expert Group 2008 ....................................................................................... 80 Systematic review of bisphosphonates in early breast cancer i 6 Discussion ..................................................................................................................... 81 7 Conclusion .................................................................................................................... 83 Abbreviations ............................................................................................................................ 84 Appendix A Contributors ...................................................................................................... 89 Appendix B Literature search strategy ................................................................................ 90 Appendix C Conference abstract literature search ............................................................ 92 Appendix D Clinical practice guideline literature search ................................................... 93 ii Systematic review of bisphosphonates in early breast cancer Tables Table 1 Criteria for determining study eligibility ....................................................................... 4 Table 2 Exclusion criteria ......................................................................................................... 5 Table 3 Included and excluded citations .................................................................................. 6 Table 4 Included systematic reviews ....................................................................................... 6 Table 5 Included randomised controlled trials (RCTs) ............................................................. 7 Table 6 Characteristics of the identified conference abstracts describing unpublished RCTs ......................................................................................................................... 10 Table 7 NHMRC dimensions of evidence8 ............................................................................. 12 Table 8 NHMRC interim levels of evidence9 .......................................................................... 13 Table 9 Quality criteria for different levels of evidence9 ......................................................... 14 Table 10 Key characteristics of included RCTs ....................................................................... 19 Table 11 Disease-free survival, recurrence-free survival, and survival free of bone metastasis ................................................................................................................. 33 Table 12 Mortality and overall survival ..................................................................................... 36 Table 13 Adverse events ......................................................................................................... 40 Table 14 Cancer recurrence and metastasis ........................................................................... 46 Table 15 Spinal BMD ............................................................................................................... 52 Table 16 BMD at locations other than the spine .....................................................................