Genetic diagnosis of breast and ovarian cancer. Cancer is one of the diseases with the greatest impact on the health of the population; in women, breast and ovarian cancer is the most prevalent. Genetic diagnosis of hereditary cancers has become a key tool for both prevention and treatment. A greater understanding of the architecture of hereditary cancer, along with substantial improvements in molecular techniques, has led to the robust clinical implementation of these tests. We'll explain a little more about them.
Hereditary breast and ovarian cancer
Breast cancer is the most common type of cancer in the female population worldwide., In fact, 1 in 8 women will develop breast cancer in their lifetime, meaning a significant portion of the population will be affected by this disease. Scientific evidence now shows that between 5 and 10% of cases are hereditary, while the rest are considered sporadic with a multifactorial component, meaning that both environmental and genetic factors play a role in their development.
The best-known genes related to hereditary breast and ovarian cancer are BRCA1 y BRCA2 , These genes have high penetrance, so having a mutation in either of them carries a high risk of developing both types of cancer during one's lifetime. That said, Only about 25% of hereditary breast and ovarian cancer cases are due to mutations in these two genes , Therefore, it is important to consider other genes when performing a genetic test to rule out the hereditary risk of this type of cancer.
Ovarian cancer , Unlike breast cancer, hepatic carcinoma has a stronger hereditary component, with an estimated 20% of cases attributed to hereditary factors. This type of cancer has a lower survival rate, making early detection crucial.
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, that is, mutations that increase the risk of cancer and are present in all cells of the body, including germ cells, and therefore can be inherited.
Penetrance indicates the manifestation of cancer in individuals with a mutation; in pan-cancer panels we generally find genes with high penetrance such as BRCA1 o BRCA2 and moderate penetrance genes such as PALB2 o ATM.
Regardless of its hereditary nature, cancer is a disease of genetic origin in which cells multiply uncontrollably, accumulating mutations. These mutations occur in a specific tissue and are therefore considered somatic mutations. The main groups of genes that can exhibit somatic mutations contributing to the development of cancer are:
- Tumor suppressor genes: protective genes that control cell proliferation.
- Oncogenes: These are proto-oncogenes that have undergone a mutation. The proto-oncogene participates in normal cell multiplication and division.
- Replication error repair genes: responsible for the maintenance and integrity of DNA.
Alterations in any of these genes can lead to abnormal cell growth, resulting in tumor cells. The first two groups have opposing functions: suppressors are negative regulators of cell growth, while the latter are key to cell proliferation and differentiation. On the other hand, mismatch repair genes, also known as error repair genes, correct errors in the DNA sequence that occur during replication.
Genetic tests to detect the risk of gynecological cancer
Genetic testing allows the identification of germline DNA variants associated with an increased risk of developing one or more types of cancer, enabling personalized clinical management for patients and their families. In recent years, we have seen genetic testing evolve from analyzing a limited set of genes targeting a single type of cancer to a more comprehensive 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. This means that although a gene is primarily associated with one type of cancer, it can also increase the risk of developing other types of hereditary cancer. This overlap makes genetic diagnosis difficult when using panels specifically designed for a particular type of cancer. Using panels that target multiple cancer types increases the likelihood of finding variants associated with hereditary cancer.
When using pan-cancer panels in clinical practice, it is also important to limit gene selection 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 beginning to become a reality today. As early as 2014, Dr. Mary-Claire King, discoverer of the relationship between genes, BRCA1 y BRCA2 and the hereditary breast and ovarian cancer syndrome, published an article in JAMA mentioning the importance of studying these two genes preventively, 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 compiles the results of 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 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, as they include the recommended medical management depending on the gene that has the mutation.
The available scientific evidence seems to highlight an issue to consider in the clinical setting: the importance of incorporating the use of preventive genetic testing into hereditary cancer screening. These tests should always be prescribed by a genetic counselor or specialist who can determine if the test is appropriate for each individual, explain its limitations, and, of course, establish the steps to follow once the results are obtained.
Genetic diagnosis
In addition to the application of genetic testing in the preventive field, the most common clinical approach is the diagnosis of mutations in patients with a family history or who even present the pathology.
In patients with breast or ovarian cancer, genetic testing provides essential information for surgery and even for possible drug treatment, such as PARP inhibitors for cases of ovarian cancer with mutations in the BRCA1 and BRCA2 genes.
Genetic testing in cancer patients allows for personalized follow-up care, since the presence of genetic mutations may indicate a risk of developing other types of cancer, and this information enables adjustments to medical management. Furthermore, the results allow for the screening of first-degree relatives who may carry the mutation to determine their risk.
Technological advancements have reduced the cost of genetic testing, making it more affordable and effective for patients today, contributing to increased survival rates and improved quality of life.
In zogen we offer a comprehensive portfolio of genetic tests for hereditary cancer aimed at both prevention and diagnosis. For more information about Zogen tests, please feel free to contact us.
Source: https://www.veritasint.com/blog/en/breast-and-ovarian-cancer-genetic-diagnosis/
