A Study of Biological, Genetic, and Constitutional Factors and Non-invasive Monitoring to Assess Personal Cancer Risks

The observational study consists of a retrospective and a prospective part. For the retrospective part 400 patients with breast tumors operated between 2000 and 2015 will be selected, of which 200 with hereditary breast tumors and 200 with non-hereditary breast tumors and with the following clinical, morphological and molecular class characteristics (luminal A and B, triple negatives) and stackable staging. The tumor tissue will be subjected to immunocytochemical investigations to study the following parameters: angiogenesis (CD31), fibroblasts (CD34 and vimentin), macrophages (CD68) and tumor associated macrophages (M1: CD11c; M2: CD163); plasma cells (CD138), T lymphocytes (CD8); Mast cells (CD117). The data will be correlated with the prognosis and with the risk of developing hereditary breast cancer. The prospective part, on the other hand, envisages the enrollment of different cohorts of patients who are initially screened in WP1. 600 patients known for breast cancer (N=200), ovarian cancer (N=200) and colorectal cancer (N=200) candidates for germline genetic testing in the context of an oncogenic consultation will be evaluated. Patients will be selected before surgery and, if they agree to participate in the study, they will sign the informed consent in an oncogenetics consultancy context. The selected patients will undergo blood sampling (5 ml in EDTA tubes) for the extraction of nucleic acids (DNA and RNA). Based on the result of germline genetic testing, patients will be classified into 3 cohorts: * COHORT 2A, subjects with hereditary inheritance (probands): the identification of about 10% (N=60) of probands out of 600 subjects examined (20 for pathology) is assumed. * COHORT 2B, subjects identified by genetic counseling as being at risk of being carriers of a hereditary neoplastic syndrome, not proven by genetic tests: a population of 60 subjects, 20 for each type of tumour, with similar clinical characteristics of age and phenotype compared to cohort 2A. * COHORT 2C, a further subgroup of patients (N=150), 50 for each type of tumor, negative results in diagnostic genetic analysis. In selected patients in cohort 2C, DNA/RNA will be analyzed for the identification of causative genetic variants in genes that have escaped routine diagnostic investigation. Moreover, a further cohort of patients will be selected, COHORT 3 which includes 250 patients undergoing radical surgical treatment and with the following characteristics: * locally advanced breast cancer with triple negative phenotype or with lobular histology (N=50); * high-grade serous ovarian carcinoma (N=50); * stage III melanoma (N=50); * stage IIB and IIIA non-small cell lung cancer (N=50); * colon cancer with lymph node involvement and vascular invasion (N=50). Patients enrolled in COHORTS 2A, 2B and 3 will undergo the following blood draws for WP2: * 20 ml in Cell-Free DNA BCT® CE tubes (Streck) for ctDNA analysis. Samples are centrifuged at 1600 (±150) g for 10 minutes at room temperature. After centrifugation, the plasma is subjected to further centrifugation for 10 minutes at 3000 (±150) g. * 20 ml in Cell Save tubes for the isolation of CTCs. * 30 ml for the study of circulating immune populations (WP3). Furthermore, the tumor tissue taken during the surgical phase will be collected and analyzed in WP4 and for the study of the microenvironment with "Next Generation Sequencing" techniques applied to the tumor as a whole and at the single cell level and to the immune populations (TILs).