The Brazilian Hereditary Cancer Network: historical aspects and challenges for clinical cancer genetics in the public health care system in Brazil

Although the majority of cancers result from complex interactions between genetic, epigenetic and environmental factors, inherited germ-line mutations with high penetrance account for approximately 5-10% of all tumors (Weitzel et al., 2010). Extrapolating these estimates to the Brazilian population, 2,850 to 5,720 of the 57,120 new breast cancer and 1,630 to 3,260 of the 32,600 new colorectal tumors are expected to be hereditary according to 2014 estimates (http://www.inca.gov.br/estimativa/2014/). During the last two decades our understanding of the molecular mechanisms of cancer has immensely increased. New technologies like new generation sequencing (NGS) and in-depth analyses of large tumor series (as the ones included in The Cancer Genome Atlas TCGA) have identified driver and associated mutations in most tumors and provided significant insights on the molecular pathways of the different stages of carcinogenesis (Ciriello et al., 2013; Liu and Zhang 2014). In the field of clinical cancer genetics, several genes directly involved in hereditary cancers have been identified and characterized and more than 50 syndromes associated to cancer predisposition have been described to date (Hodgson and Maher, 1993; Lindor et al., 2008). These discoveries led to the development of programs for Genetic Cancer Risk Assessment (GCRA) for identifying and managing patients and families with hereditary cancer. GCRA has been defined as “a specialized clinical practice that requires knowledge of genetics, oncology and patient and family counseling skills involving more provider time than most other clinical services” (Weitzel et al., 2011). GCRA programs are characteristically carried out in academic and tertiary care health centers with multidisciplinary teams providing diagnosis, genetic counseling, and frequently, long term management of patients and their relatives (MacDonald et al., 2010). Several guidelines have been recommended by professional societies in North America and Europe, like the American Society of Clinical Oncology (ASCO), the European Society of Medical Oncology (ESMO), the European Society of Human Genetics (ESHG), the National Society of Genetic Counselors (NSGC), the Oncology Nursing Society (ONS) and other health care professional organizations (like the EuroGenTest). These guidelines have outlined the basic standards for cancer risk counseling, risk assessment and genetic testing (American Society of Clinical Oncology, 2003; Trepanier et al., 2004; Dierking et al., 2013; Stoffel et al., 2014). More recently, the reduced costs of genetic tests, the possibility of multiplex gene assays and NGS have significantly improved access to GCRA programs. However, several challenges and limitations still persist for a successful, molecular diagnosis of hereditary cancer, like ethical aspects arising from unsolicited or unexpected results or absence of identifiable mutations in a significant proportion of families with hereditary cancer phenotypes (the “missing heredity” phenomenon, observed in 40-60% of families, depending on the phenotype) (Samuel et al., 2014; Tung et al., 2015).