Detection of pathogenic variants in breast cancer susceptibility genes in bilateral breast cancer

Abstract

PurposeTo investigate the frequency of germline pathogenic variants (PVs) in women with bilateral breast cancer.MethodsWe undertookBRCA1/2andCHEK2c.1100delC molecular analysis in 764 samples and a multigene panel in 156. Detection rates were assessed by age at first primary, Manchester Score, and breast pathology. Oestrogen receptor (ER) status of the contralateral versus first breast cancer was compared on 1081 patients with breast cancer withBRCA1/BRCA2PVs.Results764 women with bilateral breast cancer have undergone testing ofBRCA1/2andCHEK2; 407 were also tested forPALB2and 177 forATM. Detection rates wereBRCA111.6%,BRCA214.0%,CHEK22.4%,PALB21.0%,ATM1.1% and, for a subset of mainly very early onset tumours,TP534.6% (9 of 195). The highest PV detection rates were for triple negative cancers forBRCA1(26.4%), grade 3 ER+HER2 forBRCA2(27.9%) and HER2+ forCHEK2(8.9%). ER status of the first primary inBRCA1andBRCA2PV heterozygotes was strongly predictive of the ER status of the second contralateral tumour since ~90% of second tumours were ER− inBRCA1heterozygotes, and 50% were ER− inBRCA2heterozygotes if the first was ER−.ConclusionWe have shown a high rate of detection ofBRCA1andBRCA2PVs in triple negative and grade 3 ER+HER2− first primary diagnoses, respectively. High rates of HER2+ were associated withCHEK2PVs, and women ≤30 years were associated withTP53PVs. First primary ER status inBRCA1/2strongly predicts the second tumour will be the same ER status even if unusual for PVs in that gene.

BRCA1 and BRCA2 germline mutations in Chinese Hakka breast cancer patients

“…Bilateral breast cancer has been identified as an independent predictor for BRCA1/2 mutation. Various studies have shown that the detection rate of BRCA1/2 gene mutations can be high in patients with bilateral breast cancer [ 50 , 51 ]. Yuntao Xie et al recently developed a nomogram, BRCA -CRisk, to accurately predict the risk of contralateral breast cancer in patients with BRCA1/2 mutations [ 52 ].…”

The Revolution in Breast Cancer Diagnostics: From Visual Inspection of Histopathology Slides to Using Desktop Tissue Analysers for Automated Nanomechanical Profiling of Tumours

“…Some of the most common genetic tests in the diagnosis of breast cancer are the following: First, predictive genetic tests look for inherited mutations in genes that increase the risk of breast cancer, such as BRCA1, BRCA2, and TP53 [ 21 ]. These tests identify people with a high chance of developing breast cancer in the future.…”

DataSheet_1.pdf

“…A total of nine studies (22)(23)(24)(25)(26)(27)(28)(29)(30) presented frequencies of germline variants that allowed the following comparisons: HR-HER2+ versus TNBC (Supplementary Figure 5), HR-HER2+ versus HR+HER2-(Supplementary Figure 6), HR+HER2+ versus TNBC (Supplementary Figure 7), HR+HER2+ versus HR+HER2-(Supplementary Figure 8), and HR+HER2+ versus HR-HER2+ (Supplementary Figure 9). Moreover, eleven studies (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32) allowed the comparison of HR+HER2versus TNBC (Supplementary Figure 10). For each comparison, genes were included when a variant was reported in at least two studies.…”