Breast cancer is the cancer with the highest incidence in women worldwide, including the Netherlands, and ranks first for most cancer-related deaths in the developing world and second in the developed world 1 . The Netherlands Comprehensive Cancer Organisation (IKNL) reported 14748 invasive breast cancer diagnoses in 2018 in the Netherlands 2 . The incidence of breast cancer has increased over the years, and is expected to increase by 46% (relative to 2018) by 2040 2,3 . This increase is partly due to an aging population and lifestyle changes, e.g. obesity is associated with post-menopausal breast cancer diagnosis 3 , but also due to more sophisticated breast cancer screening strategies 4,5 .Together with screening and improved locoregional treatment (i.e., surgery and radiotherapy), adjuvant systemic therapy (AST) has led to a decrease in mortality of breast cancer patients: 10-year overall survival increased from 68% in 1991-2000 to 76% in 2001-2010 2,6 . There are different kinds of AST: endocrine, targeted, and chemotherapy. If, and what type of AST a patient receives depends on several clinicopathologic variables, such as age and tumor size, but also on the immunohistochemical (IHC) subtype of the tumor. The IHC subtype is especially important because it can be used as a predictive marker of therapy effectiveness 7 .It is classified through the expression of the estrogen-and the human epidermal growth factor-2 (HER2) receptor on the tumor. If a tumor expresses the estrogen receptor, i.e. is ER+, then endocrine therapy can be prescribed, similarly, if a tumor expresses HER2+ targeted therapy can be prescribed. Chemotherapy can be prescribed to all IHC subtypes. ER+-breast cancer represents the largest proportion of the IHC subtypes, about 80% of all breast cancer are ER+ 8 , and many of these patients receive endocrine therapy. The indication for endocrine therapy as recommended by guidelines has increased over the years, and has included increasingly favorable prognostic profiles: 23% of patients diagnosed in 1990 in the Netherlands received endocrine therapy, which increased to 56% by 2012 9 . Although survival has increased over the years, there are now concerns about overtreatment 10 . A patient can be considered overtreated if she did not derive any survival benefit from AST, because she would have died despite AST, or, alternatively, because she would have also survived without AST. A patient who is overtreated is exposed to AST-related sided effects without any survival benefit. Side effects include sexual dysfunction, cognitive
Thesis outlineThe aim of this thesis was to investigate whether breast MRI, and specifically CPE, has the potential to play a role in the personalization of endocrine therapy in ER+/ HER2-breast cancer.In Chapter 2 we start by giving an estimate of overtreatment with the current treatment strategies with data from the Netherlands and the United States of
CHAPTER Overtreatment with adjuvant systemic therapy in early breast cancer patientsPopulation-based estimates of overtreatme...