The role of bone targeted agents in early breast cancer

Breast cancer is the most common cancer among women with almost 56,000 new cases every year in the UK. Most of the new cases are diagnosed as early breast cancer (EBC) which is potentially curable. However, metastatic disease is the main cause of death in advanced breast cancer. Bone has been identified as the most common site of metastasis in breast cancer and is present in 70% of the patients with metastatic disease.
The bone targeted agents bisphosphonates (BPs) have been extensively investigated for their role in early and metastatic disease. Currently, they have been approved for the following settings:
1) Prevent bone metastasis.
2) Prevention and treatment of cancer treatment-induced bone loss (CTIBL).
3) Management of established bone metastasis.

The main aim of this MD thesis is to describe the role of BPs in EBC and give a better understanding of their use within the UK. Multiple studies have shown that if BPs are given after breast cancer surgery offer anticancer benefits. Nevertheless, these are only in postmenopausal women (natural or induced). The ZOLMENO study, a single centre proof of concept study, was set up with the aim to provide further data for the mechanism responsible for these differential effects of adjuvant BPs. Additionally, the use of these agents in EBC has only recently been approved in the UK, providing the opportunity to track their journey within the UK breast cancer practice. Two surveys (breast cancer oncologists and oncology pharmacists) were conducted with plan to describe the use of adjuvant BPs in the UK. An international collaboration was formed between our team and Australian colleagues where the UK physicians’ adjuvant BPs survey was compared to the Australian physicians’ survey, with the aim to support the adoption of these agents in Australia but also pave the way for other nations to follow the UK example. Also, with the support of Breast Cancer Now (BCN), a UK breast cancer charity, a patients’ survey was performed to gather information about the experience of patients receiving adjuvant BPs.
Early breast cancer therapies are known for their effects on bone health. In particular, antioestrogen treatment with aromatase inhibitors (AIs) have been shown to lead to bone loss and increase the risk of fractures. Subsequently, fragility fractures increase mortality and significantly affect quality of life. Therefore, prevention of CTIBL is crucial, to minimise the risk of fractures among breast cancer patients. This is highly important for older (>70 years) EBC patients where bone density is already negatively affected by age and menopause. With the aim to determine the management of bone health of older women receiving AIs for EBC in the UK, bone health data were collected from the participants of the large multicentre Bridging the Age Gap (BTAG) study .