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What genetic factors are associated with hereditary breast cancer?

Although approximately 10% - 30% of all breast cancer cases are attributed to hereditary factors, only 5%-10% of cases are correlated with a highly penetrant hereditary factor (percentage of individuals with a particular genotype that expresses the corresponding phenotype), whereas only a small fraction of these cases (4%-5%) can be explained by mutations in autosomal dominantly transmitted genes.

Germline mutations in the BRCA1 and BRCA2 genes account for approximately 50% of the total risk for hereditary breast cancer. The estimated prevalences for carriers of BRCA1/2 mutations are, respectively, 0.11% and 0.12% in the general population and between 12.8% - 16% in high-risk families, with three or more cases of breast cancer. breast or ovary.

Recent technological advances in the area of large-scale parallel sequencing have identified that the remaining 50% of breast cancer cases are due to a combination of effects produced by mutations in high, moderate and low penetrance genes. Currently, among cases diagnosed as hereditary, only 5 to 7% are recognized in specific genes with heritable mutations (BRCA1, BRCA2, TP53, PTEN, STK11, LKB1, MSH, PALB2 among others) and can be discovered in tests and exams. Several of these genes have been previously identified and associated with other neoplasms. (Table 1).

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Table1. Susceptibility Genes for Breast Cancer

What is Oncogenetics?

Oncogenetics is the field of genetics that studies the molecular biology of tumors. One of its main developments is the advent of the use of target therapy in cancer, that is, the use of drugs aimed at patients with certain genetic variants, given that therapeutic effectiveness is related to oncogenetics. Genetic evaluation in oncology occurs in the DNA of tumor tissues, called somatic analysis; or in the search for germline variants in hereditary neoplasms, about 5% to 10% of cases.

What are Hereditary Breast and Ovary Cancers (HBOC)?

Several clinical studies have established, over the last decades, a relationship between certain genes and predisposition to specific types of cancer. The association between germline mutations in the BRCA1 and BRCA2 genes and predisposition to hereditary breast and ovarian cancer (HBOC) became clear, and this was the milestone for the beginning of predictive genetic testing. Mutations in the BRCA genes account for about 5% of breast cancers and 10-15% of ovarian cancers. In addition to HBOC, more than 300 different hereditary cancer syndromes are now described. The typical phenotype of a family with HBOC is constituted by multiple cases of breast and/or ovarian cancer in women or even in men, prostate cancer, stomach, pancreas, among others. Among patients with a history of HBOC, 20-30% have mutations in BRCA1/2.

What other hereditary breast cancer predisposition syndromes?

Mutations in other genes associated with familial syndromes, in which the incidence of breast cancer is increased, account for 5% of cases. In these syndromes, breast cancer is not the primary phenotype observed. Families with Li-Fraumeni Syndrome have breast cancer at an early age. Occurrence of breast cancer, age ≤ 35 years and negativity for BRCA mutations suggest the investigation of mutation in the TP53 gene. Other genes associated with familial syndromes are: CDH1 (hereditary diffuse gastric cancer), PTEN (Cowden Syndrome), PALB2 and STK11 (Peutz-Jeghers Syndrome).

The identification of other genes, of moderate penetrance, that attribute increased susceptibility to familial cancer help to determine the risk for HBOC. Some of these genes result in overlapping phenotypes, so they may be altered in different types of cancers. In these cases, we recommend the use of panels that include genes with high and moderate penetrance, whose alteration underlies different types of cancer (ovarian, breast, endometrium, colorectal cancer, pancreas and melanoma).

Genetic tests in oncology are useful both as a diagnostic aid and to establish a prognosis and help with therapeutic choice. Currently, genetic tests are relevant in oncology, allowing, in different types of tumors, a more personalized approach. In addition, they are also used to predict the risk of developing neoplasms in individuals with a positive family history.

What are the main oncogenetic tests?

Currently, there are numerous laboratories and tests on the market to assess genetic mutations in blood or saliva. We reiterate that these tests should be ordered and analyzed by an oncogeneticist to provide adequate guidance.

a-Sequencing of BRCA1 and BRCA2 with MLPA. MLPA (Multiplex Ligation-dependent Probe Amplification) is a method capable of detecting loss (deletion) or gain (duplication) of genetic material. Through the technique of PCR (Polymerase Chain Reaction) semiquantitative multiplex, allows to analyze changes in copy number in several genes.

b- Expanded Hereditary Cancer Panel. Genetic panel of 138 genes that aims to assess the genetic risk for the development of cancer.

c- Hereditary Breast and Ovary Cancer Panel. Genetic panel of 25 to 44 genes.

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Sorocaba Medical Center


Rua Sorocaba, 464 - room 202

Tel. 21 2537-0138 / 2539-5093

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Americas Medical City

Barra da Tijuca

Av. Jorge Curi, 550 - rooms 252/253

Tel. 21 3264-4866 / 3264-4863

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