GENERAL DISCUSSION 189 8 FUTURE PERSPECTIVES A PERSONALIZED APPROACH Clinical biomarkers In addition to tumor histomorphology, IHC and molecular biomarkers, patient characteristics may be important within EC patients regarding to outcome. Therefore, it will be clinically relevant to incorporate them within risk classification groups aiming a refined personalized approach. EC has the strongest association with obesity, and about 50% of EC diagnosis can be attributed to obesity with an enormously increased incidence with a body mass index (BMI) between 30-35 kg/m3.69, 70 Risk of LNM may differ within the different BMI subgroups.71 BMI also differs in the molecular subgroups, showing POLEmut having the lowest BMI and NSMP the highest, which at least also links tumor biology to patient environment.72 Leukocytosis is frequently observed in obese patients, and could be a surrogate biomarker of obesity. Adipose tissue establishes a pro-inflammatory environment, stimulating carcinogenic cellular proliferation pathways.25,73 Overexpression of pro-inflammatory cytokines could also contribute to the development of cancer-related anemia and thrombocytosis, and may therefore be related with tumor progression and LNM.74-76 However, a clear answer about the relation between those patient characteristics (macro-environment) and tumor progression (micro-environment) still remains unclear and needs to be elucidated. In chapter 7 we evaluated in addition to the predictive relevance, the prognostic relevance of preoperative abnormal hematological parameters i.e. anemia, thrombocytosis and leukocytosis, in EC. Previously, those abnormal hematological parameters have been associated with FIGO stage III-IV and unfavorable outcome.76-83 In this study, anemia was mainly the most important prognosticator and was identified as an independent prognostic factor for DSS. Anemia could therefore be a clinical biomarker for aggressive tumor behavior. It would be interesting to evaluate the relevance of this easy clinical biomarker in addition to the molecular subgroups. In addition to obesity, and anemia, race may also be considered for the risk classification subgroups. A recent study shows that the mortality of EC is increasing more in black women compared to white women, possibly because these women have higher incidence rates of NEEC versus EEC, the cause of which is still unclear and needs to be elucidated.69 Hence future studies should evaluate whether racial disparities impact molecular subgroups in EC. Early studies in breast cancer revealed racial differences in outcome as result of an interplay between intrinsic and extrinsic factors. Intrinsic factors with germline genetics (including different molecular subgroups) and extrinsic factors includes environmental/lifestyle factors, both affecting the tumor biology.84, 85
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