NGS-Based BRCA1, BRCA2, and PALB2 Mutation Testing in Iranian Population With Breast Cancer

Background: Identification of individuals who have a pathogenic mutation in breast cancer susceptibility genes is an important step to take advantage of genetic counseling, screening, and potentially life-saving prevention strategies. Based on the National Comprehensive Cancer Network (NCCN) guideline, genetic testing is deemed suitable for breast cancer patients with young age at onset, positive family history of cancers, male breast cancer, or diagnosis with a multifocal or triple negative breast cancer. Aim: Since, it is not known what proportion of breast cancers in Iran is hereditary and related to mutations in BRCA1/2 and PALB2 genes, therefore, we screened these 3 genes in multiethnic Iranian population to determine the spectrum of the breast cancer susceptibility gene mutations and to further assess the predictive value of the hereditary breast cancer risk criteria for genetic testing. Methods: Next generation sequencing (NGS) was conducted on a population consisted of 299 and 125 breast cancer patients, with and without hereditary cancer risk criteria for genetic testing, respectively. Results: Pathogenic mutation rate was 10.36% in patients with hereditary criteria for breast cancer vs 1.6% in no criteria group ( P = 0.002). All the patients who only met the young age at onset (<40) criterion tested negative for a gene mutation. This is while patients who had only 1 hereditary criterion (OR: 5.48, 95% CI: 1.09, 52.90, P = 0.017) and patients with multiple hereditary criteria (OR: 22.5, 95% CI: 5.19, 201.31, P < 0.0001) had a significantly higher probability of finding a mutation compared with no risk-criteria group. Conclusion: The first application of NGS on Iranian breast cancer population added to the cumulative evidence that BRCA1/2 mutations are seen commonly among Iranian breast cancer patients especially those with hereditary breast cancer criteria and indicated that PALB2 should be concerned in hereditary breast cancer screening alongside BRCA1/2. Investigating the predictive potential of hereditary breast cancer risk criteria our results suggest that offering genetic testing to women with early age at onset of <40 with no other hereditary criteria, may not be cost effective and should be considered for optimization of genetic counseling and genetic testing of the Iranian population.

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Clinicopathological Features of BRCA1/2 Mutation-Positive Breast Cancer

Oncology ◽

10.1159/000515790 ◽

2021 ◽

pp. 1-8

Author(s):

Hyun-June Paik ◽

Youn Joo Jung ◽

Dong Il Kim ◽

Seungju Lee ◽

Chang Shin Jung ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Genetic Testing ◽

Cancer Patients ◽

Hereditary Breast Cancer ◽

Gene Mutations ◽

Disease Free Survival ◽

Clinicopathological Characteristics ◽

Breast Cancer Patients ◽

Positive Breast Cancer

Purpose: The BRCA1/2 gene is the most well-known and studied gene associated with hereditary breast cancer. BRCA1/2 genetic testing is widely performed in high-risk patients of hereditary breast cancer in Korea. This study aimed to investigate the clinicopathological characteristics of BRCA1/2 mutation-positive breast cancer patients. Methods: The clinical data of 188 Korean breast cancer patients who underwent genetic testing of BRCA1/2 mutation between March 2015 and February 2020 at Pusan National University Yangsan Hospital were retrospectively reviewed. The characteristics of breast cancer according to the expression of BRCA1 and BRCA2 mutations were analyzed using the Health Insurance Review and Assessment Service guideline criteria and other clinicopathological factors. Results: The factor associated with BRCA1/2 gene expression was cancer stage, and mutation expression was significantly decreased in stage I compared to stage 0 (p = 0.033; odds ratio [OR], 0.169; 95% confidence interval [CI], 0.033–0.867), and there was a tendency to increase in stage II (p = 0.780; OR, 1.150; 95% CI, 0.432–3.064). BRCA1 was significantly associated with triple-negative breast cancer (TNBC) (p = 0.004; OR, 5.887; 95% CI, 1.778–19.498). Gene expression of BRCA2 was significantly reduced under 40 years of age (p = 0.040; OR, 0.198; 95% CI, 0.042–0.930). There was no difference in disease-free survival (p = 0.900) and overall survival (p = 0.733) between the BRCA1/2 mutation-positive and -negative groups. Conclusion: In this study, the clinicopathological characteristics of breast cancer patients with BRCA1/2 gene mutations were identified. BRCA1 gene expression was highly correlated with TNBC. BRCA1/2 mutation did not have a poor prognosis regarding recurrence and death.

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HEREDITARY BREAST CANCER SURGICAL TREATMENT

Український радіологічний та онкологічний журнал ◽

10.46879/ukroj.1.2020.25-28 ◽

2020 ◽

Vol 28 (1) ◽

pp. 25-28

Author(s):

I. Motuziuk ◽

O. Sydorchuk ◽

Y. Kostiuchenko ◽

N. Kovtun ◽

P. Poniatovskyi ◽

...

Keyword(s):

Breast Cancer ◽

Genetic Testing ◽

Surgical Treatment ◽

High Risk ◽

Dna Sequencing ◽

Cancer Patients ◽

Hereditary Breast Cancer ◽

Breast Cancer Patients ◽

Type Of Surgery

Abstract. In this article we present analysis results of the surgical treatment of 56 breast cancer patients who have a high risk of heredity of the disease and meet one or more criteria of genetic testing according to the NCCN vers. 2.2019 guidelines. According to the results of genetic testing by DNA sequencing, 33 mutations were found in 12 genes in 52.7 % of patients. It has been shown that the type of surgery differs depending on the result of genetic testing.

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Germline breast cancer susceptibility genes, tumor characteristics, and survival

Genome Medicine ◽

10.1186/s13073-021-00978-9 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Peh Joo Ho ◽

Alexis J. Khng ◽

Hui Wen Loh ◽

Weang-Kee Ho ◽

Cheng Har Yip ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Cancer Patients ◽

Cancer Susceptibility ◽

Breast Cancer Susceptibility ◽

Tumor Characteristics ◽

Breast Cancer Patients ◽

Luminal B ◽

Cancer Susceptibility Genes

Abstract Background Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent. Methods Gene panel sequencing was performed for 34 known or suspected breast cancer predisposition genes, of which nine genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, and TP53) were associated with breast cancer risk. Associations between PTV carriership in one or more genes and tumor characteristics were examined using multinomial logistic regression. Ten-year overall survival was estimated using Cox regression models in 6477 breast cancer patients after excluding older patients (≥75years) and stage 0 and IV disease. Results PTV9genes carriership (n = 690) was significantly associated (p < 0.001) with more aggressive tumor characteristics including high grade (poorly vs well-differentiated, odds ratio [95% confidence interval] 3.48 [2.35–5.17], moderately vs well-differentiated 2.33 [1.56–3.49]), as well as luminal B [HER−] and triple-negative subtypes (vs luminal A 2.15 [1.58–2.92] and 2.85 [2.17–3.73], respectively), adjusted for age at diagnosis, study, and ethnicity. Associations with grade and luminal B [HER2−] subtype remained significant after excluding BRCA1/2 carriers. PTV25genes carriership (n = 289, excluding carriers of the nine genes associated with breast cancer) was not associated with tumor characteristics. However, PTV25genes carriership, but not PTV9genes carriership, was suggested to be associated with worse 10-year overall survival (hazard ratio [CI] 1.63 [1.16–2.28]). Conclusions PTV9genes carriership is associated with more aggressive tumors. Variants in other genes might be associated with the survival of breast cancer patients. The finding that PTV carriership is not just associated with higher breast cancer risk, but also more severe and fatal forms of the disease, suggests that genetic testing has the potential to provide additional health information and help healthy individuals make screening decisions.

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