Breast Cancer Evolution During Neoadjuvant Systemic Therapy

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Breast cancer is the most common female cancer in the UK and remains one of the leading causes of cancer death. Survival rates have greatly improved over the past forty years due to improvements in early diagnosis, surgical techniques, effective chemotherapy treatments, hormonal therapy, and the introduction of targeted biological treatments. However, despite this, breast cancer continues to be the 4th most common cause of cancer death in the UK and 20% of women diagnosed with this disease do not survive more than ten years after diagnosis. Systemic anticancer treatments (that is, oral or intravenous treatments such as chemotherapy, targeted therapy and immunotherapy) are routinely given before surgery (called neoadjuvant therapy) in patients with aggressive early and locally advanced breast cancer in order to shrink the cancer and make it more operable. As a result, women receiving neoadjuvant therapy often require less radical surgery to remove their cancer. Clinical trials have shown that the timing of systemic therapy (that is, whether it is given before or after surgery), does not make a difference to survival, and because of this systemic therapy before surgery is now a mainstay of breast cancer treatment. Clinical trials have also shown that the level of response in both primary breast tumour and nearby lymph nodes to systemic anticancer therapy are strongly associated with cancer relapse and survival. The presence of extensive cancer at the time of surgery is associated with a higher risk of metastatic relapse and a poor prognosis. This study will deeply analyse samples from a patient's tumour, blood, and stool, as well as data from MRI images, to identify specific features of either the patient or their cancer which could be used to predict whether (a) a treatment is likely to work and (b) once started, whether the treatment is still working. All this data will be combined together to build predictors that can identify: (a) patients who are not responding to therapy and could be directed towards different treatments and (b) patients who are responding very well to treatment and might benefit from therapy de-escalation. Additionally, by profiling these breast cancers in great detail, this project will allow us to identify new cancer vulnerabilities and drug targets that could then be used for treatment in the future.