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Adjuvant bisphosphonates in early breast cancer

Rathbone, Emma Jane (2018) Adjuvant bisphosphonates in early breast cancer. PhD thesis, University of Leeds.

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Breast cancer is commonly associated with bone metastases, with approximately 70% of patients dying from breast cancer having radiological evidence of skeletal involvement. Median survival after diagnosis on bone metastases can be 2-3 years and therefore patients are at a high risk for the development of skeletal-related events. Consequently, research in both the laboratory and the clinic has addressed the potential for bone targeted agents to reduce the risk of developing skeletal metastases. The AZURE clinical trial is an international randomised phase III clinical trial that recruited 3360 early breast cancer patients in which participants received either 19 doses of zoledronic acid (ZOL) in 5 years or observation. No other clinical trial has undertaken such an intensive schedule of adjuvant bisphosphonates and therefore the safety and longer term sequelae were imperative to investigate should the drug become a standard of care. This thesis describes sub-studies undertaken in AZURE participants to investigate i) the incidence of osteonecrosis of the jaw (a recognised complication of bisphosphonates) and oral health-related quality of life and ii) a quantitative bone scanning technique to describe the effects the intensive schedule of zoledronic acid on bone remodelling and how this changes with time. Finally, the use of bone-related biomarkers (1,25-OH vitamin D, P1NP, CTX and 1CTP) measured in serum collected at baseline (before commencing zoledronic acid) have been investigated for their prognostic and predictive potential. The principal findings described in this thesis are: i) relatively low rate of osteonecrosis of the jaw (2.1%) with no significant impact or oral health r-related quality of life; ii) patients with elevated bone turnover markers at baseline are at increased risk of bone metastasis but these markers cannot be used to identify patients who will benefit from zoledronic acid; iii) bone turnover continues to be significantly suppressed in the axial skeleton 2 years after the cessation of zoledronic acid. The quality of the safety data presented in this thesis has contributed to the introduction of bisphosphonates into standard practice in the UK and across the globe.  

Item Type: Thesis (PhD)
Keywords: Bisphosphonates, breast cancer, bone turnover markers, osteonecrosis of the jaw
Academic Units: The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds)
Identification Number/EthosID: uk.bl.ethos.766441
Date Deposited: 11 Feb 2019 16:52
Last Modified: 18 Feb 2020 12:49
URI: http://etheses.whiterose.ac.uk/id/eprint/22679

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