PURPOSE:Complex interactions occur between cancer cells and cells in the tumor microenvironment. In this study, the prognostic value of the interplay between tumor-stroma ratio (TSR) and the immune... Show morePURPOSE:Complex interactions occur between cancer cells and cells in the tumor microenvironment. In this study, the prognostic value of the interplay between tumor-stroma ratio (TSR) and the immune status of tumors in breast cancer patients was evaluated.METHODS:A cohort of 574 breast cancer patients was analyzed. The percentage of tumor stroma was visually estimated on Hematoxylin and Eosin (H&E) stained histological tumor tissue sections. Immunohistochemical staining was performed for classical human leukocyte antigen (HLA) class I, HLA-E, HLA-G, markers for regulatory T (Treg) cells, natural killer (NK) cells and cytotoxic T-lymphocytes (CTLs).RESULTS:TSR (P < .001) and immune status of tumors (P < .001) were both statistically significant for recurrence free period (RFP) and both independent prognosticators (P < .001) in which tumors with a high stromal content behave more aggressively as well as tumors with a low immune status. Ten years RFP for patients with a stroma-low tumor and high immune status profile was 87% compared to 17% of patients with a stroma-high tumor combined with low immune status profile (P < .001). Classical HLA class I is the most prominent immune marker in the immune status profiles.CONCLUSIONS:Determination of TSR is a simple, fast and cheap method. The effect on RFP of TSR when combined with immune status of tumors or expression of classical HLA class I is even stronger. Both are promising for further prediction and achievement of tailored treatment for breast cancer patients.KEYWORDS:Breast cancer; HLA; Immune cells; Prognosis; Tumor–stroma ratio Show less
Blok, E.J.; Derks, M.G.M.; Kuppen, P.J.K.; Kranenbarg, E.M.M.K.; Engels, C.C.; Liefers, G.J.; ... ; Velde, C.J.H. van de 2017
Breast cancer is the most common malignancy and the leading cause of cancer related death in women of the western world. For most women, increasing age is the primary risk factor for breast... Show more Breast cancer is the most common malignancy and the leading cause of cancer related death in women of the western world. For most women, increasing age is the primary risk factor for breast cancer. Therefore, the number of breast cancer patients is expected to further increase in the coming years. The work presented in this thesis is part of the collaborative FOCUS project, seeking insight into breast cancer disease (in the elderly), aiming to define normal tissue, breast cancer, and therapeutic sensitivity differences in observational, population-based cohorts consisting of elderly breast cancer patients. Topics discussed in this thesis are differences and clinical value of molecular differentiation, immune evasion, proliferative and apoptotic signaling; but also the predictive value of IGF1R and HER2 expression on the breast tumors. Last but not least, we discuss the effects of aging on tumorgenesis and the road to precision medicine. Only when all medical specialties bound to the care and cure of older cancer patients join forces, known as a multidisciplinary oncogeriatric battlefront, treatment goals, and implementation hereof will be achieved. Show less
Engels, C.C.; Kiderlen, M.; Bastiaannet, E.; Eijk, R. van; Mooyaart, A.; Smit, V.T.H.B.M.; ... ; Liefers, G.J. 2016