Bas van der Velden
December 2017
Promotor: M.A. Viergever
Co-supervisor: K.G.A. Gilhuijs
Abstract
This thesis presents a biomarker for breast cancer patient survival utilizing the healthy breast tissue at dynamic contrast-enhanced magnetic resonance imaging.
Traditionally, patients are treated relatively uniformly depending on the stage of the tumor. Since breast cancer is a very heterogeneous disease, substantial difference in prognosis exists between patients. Therefore, overtreatment is a serious concern; patients with a relatively good prognosis may be treated too aggressively – suffering treatment related side effects, psychological effects, and poorer cosmetic outcome – without a survival benefit.
Currently, treatment plans are established by a multi-disciplinary team of professionals based on patient and pathology characteristics. Recent developments in genetics yielded additional tools such as the Mammaprint and Oncotype DX, leading to improved patient-risk stratification. It is, however, likely that patients at risk of overtreatment still exist. Hence, new tools should be applied to identify these patients. Dynamic contrast-enhanced magnetic resonance imaging (MRI) allows for assessment of the biology of the breast and tumor, making it a potential tool for identifying new patient groups at risk of overtreatment.
The aim of this thesis was to find novel MRI biomarkers of healthy breast tissue to identify which breast cancers are life threatening – even with current treatment strategies – and which yield lower risk in the sense that they may be candidates for further treatment de-escalation. These biomarkers were investigated in the context of reducing systemic overtreatment of early breast cancer.
The functional behavior of the parenchymal tissue can be assessed after intravenous contrast injection. The contrast agent increases the signal intensity, leading to enhancement of the parenchymal tissue on MRI. The parenchymal enhancement of the healthy breast was shown to be associated with patient survival after treatment of breast cancer.
Patients with ER-positive/HER2-negative breast cancer showing pronounced enhancement of the healthy parenchymal tissue had a significantly superior survival in two independent cohorts from two different cancer centers; this was especially the case in the patients treated with endocrine therapy. The biomarker showed complementary value to current prognostic and predictive models for therapy selection of breast cancer, and can potentially be strengthened by adding genetic ER-pathway information of the tumor. Therefore, it is a promising new tool in assessing which patients are potential candidates for treatment de-escalation.