Clinical, histopathological and molecular characterization of liver metastases from patients with breast cancer

Surgery is the only potentially curative option for patients with liver metastases (LM) from solid tumors. However, a substantial proportion of patients operated with a curative-intent develop rapid tumor recurrence after LM resection, emphasizing the need for predictive biomarkers when considering this aggressive and morbid surgery. Accordingly, the identification of better selection criteria for surgery is a major objective to improve the global management in these patients. Surgical curability of LM depends primarily on cancer biology, resulting from interactions between tumor biology and host responses. The patients who are likely to benefit the most from surgery for LM are those presenting a oligometastatic (OLM) profile, as defined as tumors with limited metastatic capacity, developing few metastases in a limited number of secondary sites. Currently the markers of OLM disease have not been accurately established. The clinical, histological, immune and genetic parameters with a prognostic impact currently demonstrated remain poorly contributive to distinct the patients that will benefit from surgery from those who will not. Accordingly, the reliable identification of OLM patients could be made only on the basis of favorable post-surgical outcome (i.e. long-term survival or cure after surgical resection of LM). Retrospective studies are therefore pivotal to explore and to validate biomarkers of real OLM that may benefit from resection and, in contrast, of occult diffuse or polymetastatic diseases who should not be considered for curative-intent therapy. In the present project, we propose to develop a ULB multidisciplinary platform aiming at evaluating several parameters and candidate biomarkers for OLM in a retrospective cohort of 450 patients operated for LM. These patients are identified in a data base prospectively collected since 2005. In these patients, post-surgical outcome will be correlated with various parameters, including clinical data and, at primary tumor and the LM levels, histological data (tumor differentiation, lymphovascular invasion, mutational status, growth pattern), immune parameters (T cell infiltrates, tertiary lymphoid structures, checkpoint molecules) and genomic data (exome sequencing). This collaborative work will be performed in multidisciplinary ULB group including clinical teams, hospital laboratories and laboratories. Presumably, the identification of new biomarkers will be able to improve the treatment individualization in patients with LM, such as optimizing surgical selection and avoiding unnecessary surgery. Furthermore, a better characterization of the individual tumor biological profiles will be helpful to develop innovative approaches (i.e. adjuvant surgery in patients with unresectable LM but good prognostic factors, treatment adaptation according to the particular evolution of biological parameters during the time and treatment, effect of new treatments, such as immunotherapy, on tumor biology). In parallel with this study, a prospective collection of different samples will be organized in patients operated for LM (fresh liver tissue from LM and non-tumor liver, blood and stools) in order to validate and explore in depth the hypothesis generated in the retrospective part.