What question did this study set out to answer?

The study aims to characterize the germline genomic profile of luminal breast cancer in Brazil and assess the prevalence of pathogenic variants.

May 24, 2026Open Access

412eP The clinical behavior of different molecular subtypes of breast cancer - a retrospective study

Key Points

The study aims to characterize the germline genomic profile of luminal breast cancer in Brazil and assess the prevalence of pathogenic variants.
Analyzed whole-exome sequencing data from 73 women with luminal breast cancer and 177 controls.
Processing followed GATK Best Practices and stringent filtering to identify high-confidence variants.
Reclassification of cases based on identification of moderate-to high-penetrance pathogenic variants.
Identified 350,686 high-confidence variants in the luminal breast cancer cohort, including 13,020 novel variants.
Carriers of pathogenic variants in breast cancer susceptibility genes were significantly higher in cases (17.8%) than controls (7.9%) (OR: 2.59; p=0.02).
Reclassification of cases increased the proportion of HBOC syndrome from 5.5% to 16.4%.

Abstract

Background: Breast cancer (BC) is one of the leading neoplasms among women worldwide, with the luminal subtype (LBC) being the most prevalent.However, Brazilian genomic data remains scarce, limiting precision oncology approaches, especially among women who do not carry pathogenic or likely pathogenic (P/LP) genetic variants (GVs) in genes related to hereditary breast-ovarian cancer (HBOC) syndromes.This study aimed to characterize the germline genomic profile of an unselected cohort of LBC in Parana, Brazil, using whole-exome sequencing (WES) data, and compared it with controls. Methods:We analyzed germline WES data from 73 women with LBC and 177 controls from Curitiba, Brazil.Data processing followed GATK Best Practices and stringent filtering (VQSR and CEGH Filter) to identify high-confidence GVs.Annotation was carried out on ANNOVAR.We assessed the presence of P/LP GVs in BC susceptibility genes (BCSGs) in both groups.Cases were also clinically reclassified based on the identification of moderate-to high-penetrance P/LP GVs in HBOC genes. Results:We identified 350,686 high-confidence GVs in the LBC cohort, including 13,020 novel variants absent from major public databases (gnomAD, 1kGP, ABraOM).The frequency of carriers of P/LP GVs in BCSGs was significantly higher in cases (17.8%) compared to controls (7.9%) (OR: 2.59; p=0.02), and carrier status was strongly associated with relevant cancer family history (OR: 4.29; p=0.02).Notable findings included the BRCA2 c.475+1G>A GV in a patient of Japanese descentlikely the first report in Braziland the BRCA2 c.6656C>G GVrecurrent in Brazil, yet not reported in Paran.WES data led to the reclassification of 8 cases previously stratified as familial or sporadic BC.The proportion of HBOC syndrome in the LBC cohort increased from 5.5% to 16.4% after reclassification.Notably, four clinically sporadic cases were reclassified as HBOC syndrome. Conclusions:Our study established a significant regional genomic reference and demonstrated that WES refines diagnosis beyond clinical criteria.The identification of P/LP GVs in clinically sporadic cases supports broader genomic testing to improve genetic counseling and therapeutic management in Southern Brazil.

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