Differential Profile of BRCA1 vs. BRCA2 Mutated Families: A Characterization of the Main Differences and Similarities in Patients.

Gabriela Carvalho Fernandes,Edenir Inêz Palmero,Cristovam Scapulatempo-Neto,Aline Silva Coelho,Paula Silva Felicio,Rodrigo Augusto Depieri Michelli

doi:10.31557/apjcp.2019.20.6.1655

Gabriela Carvalho Fernandes, Edenir Inêz Palmero + Show 4 more

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https://doi.org/10.31557/apjcp.2019.20.6.1655

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Abstract

The identification of families at-risk for hereditary breast cancer (BC) is important because affected individuals present a much higher cancer risk than the general population. The aim of this study was to identify the most important factors associated with the presence of a pathogenic BRCA1/BRCA2 mutation. Family history (FH), histopathological and immunohistochemical characteristics were compared among BC women with pathogenic BRCA1/BRCA2 variants; VUSs in BRCA1/BRCA2; BRCA1/BRCA2 WT and sporadic BC. The most significative differences observed concerned the molecular subtype of the tumors, age at cancer diagnosis and FH of cancer. The presence of bilateral breast cancer (BBC), number of BC cases and the presence of ovarian cancer (OC) increased (respectively) 5.797, 5.033 and 4.412 times the risk of being a BRCA1/BRCA2 mutation carrier. Besides, women with BRCA1 or BRCA2 mutations presented different tumor and FH profiles. The main characteristics associated with a BRCA1 mutation were triple negativity (OR: 17.31), BBC history (OR: 4.96) and occurrence of OC (OR: 4.32). There were no major discerning components associated with BRCA2 mutations. Thus, we conclude that tumor pathology and FH of cancer might be considered together at the time of genetic testing mainly in countries where access to genetic testing is still restricted.

Highlights

Cancer has been considered a public health problem for some time in developed and developing countries (UICC, 2016; WHO, 2016)
History (FH), histopathological and immunohistochemical characteristics were compared among breast cancer (BC) women with pathogenic BRCA1/BRCA2 variants; variants of unknown significance (VUS) in BRCA1/BRCA2; BRCA1/BRCA2 WT and sporadic BC
When Group 1 was stratified according to mutated gene, we observed that, among the triple negative tumors, 91.6% had a pathogenic mutation in BRCA1, and only 8.4% in BRCA2

Summary

Introduction

Cancer has been considered a public health problem for some time in developed and developing countries (UICC, 2016; WHO, 2016). Of the breast cancer (BC) cases diagnosed each year, it is estimated that 5% to 10% are inherited. It is believed that the BRCA1/BRCA2 genes are responsible for about 15%-25% of all cases of hereditary breast and ovarian cancer (Easton, 1999; Couch et al, 2014; Mehrgou and Akouchekian, 2016). Studies have reported an increased risk of male breast cancer associated with germline mutations in BRCA1, it represents a lesse frequent association than that with BRCA2 germline mutations (Struewing et al, 1995; Milne et al, 2008). The BRCA2 gene increases the risk of developing multiple tumors, such as: tumors of the biliary tract, bladder, esophagus, pancreas, prostate, stomach, melanoma, hematopoietic system, oral cavity and pharynx (Breast Cancer Linkage, 1999; Risch et al, 2006)

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