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Improving treatment for breast cancer patients who develop resistance

Professor Mitch Dowsett. Budgeted cost: £165,803. Started August 2018.

Project Summary

After surgery for breast cancer, most postmenopausal women are treated with drugs called aromatase inhibitors (AIs), that aim to stop the production of estrogen. AIs reduce the likelihood of the patient dying from breast cancer by about 40%. However, some women become resistant to AIs and the cancer returns. To improve treatment for these patients, we need to fully understand the molecular makeup of the tumours that become resistant to AIs. In this study, the team will access a uniquely large collection of tumour samples. All these patients received an AI for two weeks before surgery in the POETIC trial (see below). The team will compare the molecular makeup of tumours that responded to AIs, to those that developed resistance. By establishing the differences between these tumours, it may then be possible to target the resistance pathways in individual patients. Comparing the molecular makeup of the tumours requires a lengthy and highly skilled process to extract ribonucleic acid (RNA). Each sample is dissected carefully under a powerful microscope using a very fine needle. 


The team now have all the RNA sequencing data, which was delayed due to the pandemic. They are delighted with the quality of the data they received on the 452 samples of RNA that were extracted. The preliminary analyses indicate that immune characteristics of the tumours are the main feature associated with resistance to AIs. The patients in the study all had cancers that are hormone dependent (ER positive) and the results are very different from those found in tumours that do not possess estrogen receptors. The continuing analysis will aim to determine the specific immune features that dominate this association with resistance, and will consider if interventions can be identified that could block any immune-related resistance. 

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