Multimodal assessment of response to neoadjuvant chemotherapy in breast cancer

Abstract

Neoadjuvant chemotherapy (NAC; chemotherapy administered before surgery) is increasingly used in the treatment of non-metastatic breast cancer. However, a significant proportion of patients’ tumors respond insufficiently to NAC. On the other hand, some breast cancer patients are currently overtreated with chemotherapy. Both groups experience unnecessary side effects as a result. To avoid these side effects while optimally treating the tumor, therapy must be tailored to each individual. For this, an accurate method for evaluating the response to NAC prior to surgery is essential. Ideally, this method should be minimally invasive to reduce the burden on the patient as much as possible. The research in this thesis focuses on developing such a method by combining various factors. The results show that the accuracy of radiological magnetic resonance imaging (MRI) assessments in evaluating response to NAC depends on the breast cancer subtype and the MRI's magnetic field strength. Additionally, we demonstrate that combining blood tests (so-called “liquid biopsies”) with tumor characteristics and breast MRI provides more predictive information on response likelihood than these factors do independently. Furthermore, the combination of immune cell presence in the tumor and tumor size observed on MRI improves response assessment. Finally, we show that a new method, which scores digitized microscopic images of the tumor based on the relationship between the tumor and its immune environment, is related to the response to NAC. In conclusion, the research in this dissertation demonstrates that combining various biomarkers can improve the assessment of response to NAC in breast cancer patients, bringing individualized breast cancer treatment one step closer.