Optimizing the Tailored Treatment of Breast Cancer

Background: Breast cancer is a diverse disease. Over the past 3 decades it has been increasingly appreciated that therapy should be targeted to specific patient and tumour characteristics. In recent years the evaluation of tailored therapy has been dominated by the development of new drug therapy which when successful has been marketed at a high price. There have been few successful attempts to optimize currently available therapies. This thesis explores the optimization of currently available therapies in three domains: efficacy, toxicity and supportive care. Methods: Three independent studies were undertaken. First, a prospective cohort study was conducted to assess the impact of re-biopsy of recurrent breast cancer on physician choice of therapy and on patient satisfaction. The second study comprised a systematic review and meta-analysis of randomized trials exploring toxicities associated with different endocrine therapy options for early breast cancer with the aim of identification of patients who may be harmed by certain drugs. Finally, a randomized feasibility study was conducted to evaluate de-escalated intravenous bisphosphonates in women with low-risk metastatic breast cancer to bone. Results: All studies met their objectives in showing that the tailored use of available therapies can be optimized. The prospective study of the impact of re-biopsy showed that treatment decisions were modified in 14% of women. Patient satisfaction with the process of re-biopsy was high. The meta-analysis of toxicities of endocrine therapy identified cardiovascular disease as a statistically significant toxicity of aromatase inhibitors, thereby suggesting that those with established cardiovascular disease or risk factors thereof should reduce their exposure to these drugs. Finally, the randomized feasibility study showed that it is possible to conduct randomized trials of de-escalated bisphosphonates in women with low-risk breast cancer and there was no signal that reducing the frequency of treatment was associated with untoward outcomes. Conclusions: It is possible to optimize the tailored therapy of breast cancer using currently available treatments. This may lead to improved patient outcome while using existing resources. Further studies assessing the optimization of other treatments are warranted.Ph