Grant: Fellowship - PA: CIHR/Rx&D - CAMO Research Program

Bone is the most common site of metastatic spread of breast cancer. The consequences of bone metastases include pain, poor mobility, a reduced quality of life and worsening survival. Patients are also at a considerable risk of skeletal related events (SREs) such as needing surgery and/or radiotherapy to bone, pathological fractures, spinal cord compression, and hypercalcemia. Avoiding such complications is therefore essential. Bisphosphonates are a class of drugs that are highly effective in reducing bone breakdown. They are widely used in patients with bone metastases to try and minimize skeletal complications and are considered the standard of care in such patients. However, despite their extensive use, about a third of patients with bony metastatic disease will still go on to experience a SRE, and there is no evidence they prolong survival. Innovative strategies to enhance their effectiveness are therefore needed. We have previously performed studies that would suggest that the cheap and widely available antibiotic, doxycycline, might well increase the anti-cancer effects of bisphosphonates in patients. A previous clinical study looked at the effects of doxycycline as a single agent in women with breast cancer that has spread to the bones and showed some modest efficacy. Based on our work, we hypothesize that adding doxycycline to the bisphosphonate treatment of patients will increase the anti-cancer activity of bisphosphonates. The results of this study could help us individualize the care of patients and also reduce the mortality and morbidity associated with bone metastases.