Optimizing systemic therapy in metastatic breast cancer:implementation in daily practice and exploration of new drug targets

This thesis aims to study several aspects regarding metastatic breast cancer treatment. Approximately 15% of breast cancers express the HER2 receptor. This HER2 positivity makes it possible to treat patients with trastuzumab. Trastuzumab is a monoclonal antibody directed against HER2. Treatment and survival characteristics of patients with HER2 positive metastatic breast cancer are studied. Data of patients in the northern part of the Netherlands who have been treated with trastuzumab for metastatic breast cancer are collected by the Netherlands Cancer Registry. Tumor material of the primary breast tumors are also collected. The HER2 status has been determined using the most recent diagnostic criteria. Most of the tumors are indeed HER2 positive. It seems to be cost-effective to use a confirming diagnostic test in tumors of patients who are tested HER2 positive with the standard diagnostic test. This will also reduce the number of patients who are unfairly treated with trastuzumab. Most of the selected patients have been treated with the registered combination of trastuzumab with chemotherapy. Survival of these patients is comparable with the survival found in the previous conducted clinical trials. A limited number of patients has been treated with trastuzumab and vinorelbine containing chemotherapy. This combination was not registered for this indication, however eventually this combination has also been proven effective. Furthermore the interaction between the androgen receptor and the immune microenvironment in HER2 positive breast tumors has been studied. Furthermore the tumor micro environment in males with breast cancer has been explored