3 Frequency of Germline Variants in Breast Cancer Predisposing Genes: Genetic Background of Brazilian Women With Breast Cancer

Publication
Article
Miami Breast Cancer Conference® Abstracts Supplement39th Annual Miami Breast Cancer Conference® - Abstracts
Volume 36
Issue suppl 3
Pages: 29

Background

Five percent to 10% of breast cancer cases present strong hereditary components; to date, several genes have been associated with breast cancer predisposition. The population background has to be considered, combined with other criteria, to assign pathogenicity to germline variants following the American College of Medical Genetics (ACMG) guidelines. However, there is a bias in large databases against underrepresented admixed populations, such as Brazilians, which makes it difficult to accurately interpret the clinical relevance of germline variants. To contribute to the characterization of the genetic background of breast cancer predisposition in the Brazilian population, we evaluate the frequency and spectrum of germline variants of breast cancer susceptibility genes in a cohort of Brazilian patients with breast cancer.


Material and Methods

Two hundred and five unrelated women with breast cancer were tested for germline variants in breast cancer predisposition genes between 2014 and 2021 in 2 Brazilian centers: the Human Genome and Stem Cell Research Center (n = 150) and the Institute of Fetal Medicine and Human Genetics of São Paulo (n = 55). Of the 205 women, 108 (52.7%) were diagnosed at 45 years or younger; 44.91% had a positive family history, defined as 1 or more first- or second-degree relatives diagnosed with breast or ovarian cancer. Genetic testing was performed using custom panels containing up to 37 breast cancer-predisposing genes. We selected only variants with frequency less than 0.5% in an international (Genome Aggregation Database) and a Brazilian population database (Online Archive of Brazilian Mutations). Filtered variants were classified as pathogenic (P), likely pathogenic (LP), or variant of uncertain significance (VUS) using the ACMG 2015 guidelines.


Results

Thirty-seven patients were found to carry P/LP variants (18.1%), and a VUS was detected in 33 (16.1%). Twenty of the P/LP variants affected the BRCA1 and BRCA2 genes, and the remaining 17 patients carry variants mapped to ATM, BRIP1, CHEK2, FANCD2, MUTYH, RAD51C, RAD51D, PALB2, and TP53 genes. The BRCA1 c.5074+2T>C pathogenic variant was identified in 3 patients, which represents 8.1% of the total molecular diagnosis (P/LP). It is interesting to note that this variant is absent from consulted population databases.


Conclusions

Our findings contribute to the characterization of the genetic background of breast cancer predisposition in the highly admixture Brazilian population as a useful resource to discriminate among deleterious variants.


Funding: This work was funded by FAPESP-CEPID (2013/08028-1) and CNPq Grants: CNPq (307611/2018-3), INCT-CETGEN (573633/2008-8).

Author Affiliations:

Gabriel Bandeira do Carmo,1* Monise Lazar,1 Suzana Ezquina,1 Guilherme Yamomoto,1 Thomaz Gollop,2 Mayana Zatz,1 Maria Passos-Bueno,1 Ana Krepischi,1 Oswaldo Keith Okamoto1

1Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil.
2Department of Gynecology and Obstetrics, Faculty of Medicine of Jundiai, São Paulo, Brazil.

*Corresponding author: gbcbandeira@usp.br

Articles in this issue

15 COVID-19 Disease Course in Immunocompetent and Immunocompromised Patients  in a Breast Cancer Registry
15 COVID-19 Disease Course in Immunocompetent and Immunocompromised Patients in a Breast Cancer Registry
37 The Routine Use of Bioimpedance Spectroscopy Measurements in the Clinic as a Surrogate for Bone Mineral Content in Oncology Patients: Practical Application of the SOZO Device
37 The Routine Use of Bioimpedance Spectroscopy Measurements in the Clinic as a Surrogate for Bone Mineral Content in Oncology Patients: Practical Application of the SOZO Device
18 Psychosocial Wellbeing and Health Care Resource Utilization Among Patients With Breast Cancer During COVID-19
18 Psychosocial Wellbeing and Health Care Resource Utilization Among Patients With Breast Cancer During COVID-19
43 Early Detection of Breast Cancer–Related Lymphedema: Accuracy of Indocyanine Green Lymphography Compared With Bioimpedance Spectroscopy  and Symptoms
43 Early Detection of Breast Cancer–Related Lymphedema: Accuracy of Indocyanine Green Lymphography Compared With Bioimpedance Spectroscopy and Symptoms
3 Frequency of Germline Variants in Breast Cancer Predisposing Genes: Genetic Background of Brazilian Women With Breast Cancer
3 Frequency of Germline Variants in Breast Cancer Predisposing Genes: Genetic Background of Brazilian Women With Breast Cancer
44 Implementation of a Novel Radiopaque Filament Marker at a Single Breast Cancer Surgery Center
44 Implementation of a Novel Radiopaque Filament Marker at a Single Breast Cancer Surgery Center
39TiP The PREDICT Registry: A Prospective Registry Study to Evaluate the Effect of a Predictive Assay on Treatment Decisions in Patients withDCIS Following Breast Conserving Therapy
39TiP The PREDICT Registry: A Prospective Registry Study to Evaluate the Effect of a Predictive Assay on Treatment Decisions in Patients withDCIS Following Breast Conserving Therapy
38 Clinicopathological Risk Factors, Poorly Stratified Baseline Risk, and RT Benefit Compared to DCISionRT in Patients With Ductal Carcinoma in Situ
38 Clinicopathological Risk Factors, Poorly Stratified Baseline Risk, and RT Benefit Compared to DCISionRT in Patients With Ductal Carcinoma in Situ
28 Case Series: Imaging Appearance of Non–Breast Cancer Solid Masses in the Male Breast
28 Case Series: Imaging Appearance of Non–Breast Cancer Solid Masses in the Male Breast
20 Evaluating Number, Age, and Radiographic BIRADS of Patients Visiting Mammography Unit in Baghdad, Iraq, in 2019, 2020, and 2021: A Retrospective Study
20 Evaluating Number, Age, and Radiographic BIRADS of Patients Visiting Mammography Unit in Baghdad, Iraq, in 2019, 2020, and 2021: A Retrospective Study
5 Feasibility of WF-OCT as an Adjunct to Intraoperative Specimen X-ray for Breast Conservation Surgical Specimens
5 Feasibility of WF-OCT as an Adjunct to Intraoperative Specimen X-ray for Breast Conservation Surgical Specimens
41 A Single-Centre Report on the Upgrade Rate of Complex Sclerosing Lesions of the Breast
41 A Single-Centre Report on the Upgrade Rate of Complex Sclerosing Lesions of the Breast
45 The Informed Consent Experience for Breast Cancer Surgery and Its Association With Patient Satisfaction
45 The Informed Consent Experience for Breast Cancer Surgery and Its Association With Patient Satisfaction
29 The Effect of Personality Type on Satisfaction With Information Exchange in Breast Cancer Patients
29 The Effect of Personality Type on Satisfaction With Information Exchange in Breast Cancer Patients
36 Are Positive Margins in DCIS a True Indication of Inadequate Surgery?
36 Are Positive Margins in DCIS a True Indication of Inadequate Surgery?
Related Content