Interplay between gene-expression profiling and adjuvant systemic treatment decision-making in early stage breast cancer patients

Abstract

Adjuvant systemic treatment (AST) has improved outcome for breast cancer patients. However, not every breast cancer patient benefits from AST. Therefore, clinical treatment guidelines have been developed to distinguish those patients in whom the benefits of AST outweigh the negative effects based on their clinicopathological profile. In the first part of this thesis we describe the increased use of AST in Dutch early stage breast cancer patients on a nation-wide level under the influence of evolving clinical treatment guidelines. Furthermore, we demonstrate that guidelines are not always followed and that especially undertreatment (i.e. not receiving AST despite a guideline recommendation) is common. Clinicopathological factors do not always accurately identify those patients in whom AST is beneficial. In recent years gene-expression profiles (GEPs) have been developed to better identify those patients in whom AST is beneficial. In the second part of this thesis we describe how GEPs are currently deployed, the impact on the administration of adjuvant chemotherapy and chemotherapy decision-making in early stage breast cancer patients on a nationwide level. Concurrent with the introduction of GEPs in clinical practice, four molecular subtypes of breast cancer were identified which are associated with breast cancer outcome. These subtypes are increasingly used in the AST decision-making process. Pathological assessment of hormone receptor status, Ki67 status and Her2-Neu status can be used as a surrogate to distinguish between these molecular subtypes. In the last part of this thesis reveal a high discrepancy between molecular subtyping based on pathological assessment or a gene-expression test.