Genetic tools for breast cancer detection
Veritas Intercontinental
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Breast cancer is the most frequent type of cancer in the female population worldwide, in fact 1 in 8 women will develop breast cancer during their lifetime, so a very important part of the population will be affected by this pathology. Today there is scientific evidence showing that between 5 and 10% of cases are hereditary in origin, while the rest are considered sporadic with a multifactorial component, i.e. both environmental and genetic factors are involved in its development.
The best known genes related to hereditary breast cancer are BRCA1 and BRCA2, these genes have a high penetrance so that having a mutation in either of them means a high risk of the cancer throughout life. That said, only about 25% of cases of hereditary breast cancer are due to mutations in these two genes, so it is important to consider other genes when performing a genetic test to rule out the hereditary risk of this type of cancer.
Genetic origin of the disease
When we refer to genetic susceptibility to hereditary cancer we are talking about the presence of mutations in germline DNA, i.e. mutations that increase the risk of cancer and are present in all cells of the body, including germ cells, and can therefore be inherited.
Penetrance indicates the manifestation of cancer in individuals with a mutation, in pan-cancer panels we generally find genes of high penetrance such as BRCA1 or BRCA2 and genes of moderate penetrance such as PALB2 or ATM.
Regardless of the hereditary character, cancer is a disease of genetic origin in which cells multiply in an uncontrolled manner accumulating mutations. These mutations occur in a specific tissue and are therefore considered somatic mutations. The main groups of genes that can present somatic mutations contributing to the development of cancer are:
The presence of alterations in any of these genes can lead to abnormal growth of cells, which become tumor cells. The first two groups have opposite functions, since the suppressors are negative regulators of cell growth, while the latter are key to cell proliferation and differentiation. On the other hand, error repair genes, also known as MisMatch Repair genes, correct errors in the DNA sequence that occur during replication.
Genetic testing for cancer risk
Genetic testing allows us to identify germline DNA variants associated with an increased risk of developing one or more types of cancer, which makes it possible to adapt the clinical management of patients and their families. In recent years we have seen how genetic testing has evolved from analyzing a limited set of genes targeting a single type of cancer to a more complete analysis targeting the most common hereditary cancers.
The main reason for the clinical use of pan-cancer panels is the genetic overlap that exists in the development of hereditary cancer, i.e. although a gene is mainly related to one type of cancer it can also increase the risk of presenting other types of hereditary cancer. This overlap makes genetic diagnosis difficult when we use specific panels targeted to a certain type of cancer. Using panels oriented to several types of cancer increases the probability of finding variants related to hereditary cancer.
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When using pan-cancer panels in clinical practice, it is also important to limit the selection of genes to those with high or moderate penetrance, with sufficient scientific evidence, or whose medical management is described in clinical guidelines.When using pan-cancer panels in clinical practice, it is also important to limit the selection of genes to those with high or moderate penetrance, with sufficient scientific evidence, or whose medical management is described in clinical guidelines.
Preventive genetic screening
The preventive clinical utility of genetic testing is starting to become a reality today. Already in 2014 Dr. Mary-Claire King, discoverer of the relationship between the BRCA1 and BRCA2 genes and hereditary breast and ovarian cancer syndrome, published an article in JAMA mentioning the importance of studying these two genes in a preventive manner, due to the high prevalence of this type of cancer in the female population.
Since then, other studies have been published, such as the one that includes the results of the Healthy Nevada Project, which concluded that around 67% of women with pathogenic or probably pathogenic variants did not meet the criteria for a genetic test to detect hereditary breast and ovarian cancer, or another relevant finding, such as that around 77% of the participants with pathogenic or probably pathogenic variants related to Lynch syndrome did not meet the criteria for a genetic test.
The NCCN (National Comprehensive Cancer Network) guidelines are an important support for the preventive clinical management of patients with mutations related to breast and ovarian cancer since they include the recommended medical management depending on the gene that presents the mutation.
The available scientific evidence seems to highlight an issue to be considered in the clinical setting: the importance of incorporating the use of preventive genetic testing for hereditary cancer screening. This type of testing must always be prescribed by a genetic counselor or specialist who can determine whether the test is appropriate for each individual, inform about its limitations and of course establish the steps to follow once the results are obtained.
In addition to the application of genetic testing in the preventive setting, the most common clinical approach is the diagnosis of mutations in patients with a family history or even presenting the pathology.
Genetic studies in cancer patients make it possible to adapt their follow-up, since if they present genetic mutations they may be at risk of presenting other types of cancer, and knowing this information it is possible to adapt medical management. In addition, the result allows the study of first-degree relatives who may present the mutation, in order to determine if they are at risk.
Advances in technology have made it possible to reduce the cost of genetic tests, which are now more affordable and more effective for the patient, contributing to increased survival and quality of life.
Veritas offers the specialist a complete portfolio of genetic tests for hereditary cancer oriented to both preventive and diagnostic approaches. For more information visit veritasint.com