BRCA1 and BRCA2 germline mutations in Korean breast cancer patients at high risk of carrying mutations

30 Background: PALB2 has been identified as a breast cancer susceptibility gene conferring ~ 2-4 fold increased risk of breast cancer. A number of studies have estimated the PALB2 mutation prevalence to range from 0.5% - 2.9% in populations of breast cancer patients. We performed an analysis to determine the PALB2 mutation prevalence in a large U.S. referral testing population. Methods: DNA samples were anonymized from two subsets of patients: 955 early onset breast cancer patients with severe family history, and 524 patients with later onset of breast cancer and/or less severe family history. All patients were negative for deleterious sequence mutations or large rearrangements in BRCA1 and BRCA2. Results: We identified 10 disease associated PALB2 mutations in the high risk group of 955 patients and 2 deleterious PALB2 mutations in the lower risk group of 524 patients. Identified PALB2 mutations included 8 nonsense, 3 frameshift mutations and a splice site mutation. The mutation prevalence for the high risk population was 1.05% (95% C.I., 0.5 -1.92) whereas that for the lower risk population was 0.38% (95% C.I., 0.05-1.37). The observed rate of PALB2 variants of unknown significance (VUS) identified in this study was ~5% (78 VUS were in 75 of the 1479 patients that were tested). Our variant classification program which successfully decreased the VUS rate in BRCA1 and BRCA2 is similarly expected to enhance mutation classification on an on-going basis for PALB2 genetic testing. Conclusions: Genetic testing for PALB2 may be indicated as a reflex test for breast cancer patients who test negative for BRCA1 and BRCA2.

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Clinical Characteristics of Korean Breast Cancer Patients Who Carry Pathogenic Germline Mutations in Both BRCA1 and BRCA2: A Single-Center Experience

Cancers ◽

10.3390/cancers12051306 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1306

Author(s):

Joon Young Hur ◽

Ji-Yeon Kim ◽

Jin Seok Ahn ◽

Young-Hyuck Im ◽

Jiyun Lee ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Triple Negative ◽

Cancer Susceptibility ◽

Germline Mutations ◽

Breast Cancer Patients ◽

Single Center ◽

Brca1 And Brca2 ◽

Single Center Experience ◽

Cancer Susceptibility Genes

There are few reports of breast cancer patients who carry germline mutations in both germline breast cancer susceptibility genes 1 (gBRCA1) and 2 (gBRCA2). In this study, we analyzed the clinical, pathological, and genomic characteristics of Korean breast cancer patients with both gBRCA1 and gBRCA2 mutations. Medical records of patients who received gBRCA1 and gBRCA2 testing at Samsung Medical Center between January 2007 to October 2018 were retrospectively reviewed. Genomic DNA was isolated from peripheral blood leukocytes. Among a total of 2720 patients, four patients with both gBRCA1 and gBRCA2 mutations were identified (4/2720; 0.14%). Seven patients who had a gBRCA1 mutation and gBRCA2 variants of uncertain significance (VUS) were also identified. In those patients with both gBRCA1 and gBRCA2 mutations, the mean age at diagnosis for breast cancer was 36 years (range, 31–43 years). All four tumors were infiltrating ductal carcinomas and three of the tumors were estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2-negative (triple-negative). All four patients who carried germline mutations in both BRCA1 and BRCA2 had a family history of breast/ovarian cancer. Pathologic stage was II in three patients and I in one patient. Breast cancer patients with both gBRCA1 and gBRCA2 mutations were rare, young at diagnosis, and all but one tumor was triple-negative based on our single-center experience.

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Prevalence and Penetrance of BRCA1 and BRCA2 Germline Mutations in Colombian Breast Cancer Patients

Scientific Reports ◽

10.1038/s41598-017-05056-y ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 13

Author(s):

D. Torres ◽

J. Lorenzo Bermejo ◽

M. U. Rashid ◽

I. Briceño ◽

F. Gil ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Germline Mutations ◽

Breast Cancer Patients ◽

Brca1 And Brca2

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BRCA1 and BRCA2 germline mutations in 85 Iranian breast cancer patients

Familial Cancer ◽

10.1007/s10689-011-9477-3 ◽

2011 ◽

Vol 11 (1) ◽

pp. 57-67 ◽

Cited By ~ 10

Author(s):

Fatemeh Keshavarzi ◽

Gholam Reza Javadi ◽

Sirous Zeinali

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Germline Mutations ◽

Breast Cancer Patients ◽

Brca1 And Brca2

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Effectiveness of Neoadjuvant Therapy with Platinum-Based Agents for Patients with BRCA1 and BRCA2 Germline Mutations – A Retrospective Analysis of Breast Cancer Patients Treated at MMCI Brno

Klinicka onkologie ◽

10.14735/amko2019s31 ◽

2019 ◽

Vol 32 (Suppl 2) ◽

Author(s):

Miloš Holánek ◽

Ondřej Bílek ◽

Rudolf Nenutil ◽

Tomáš Kazda ◽

Iveta Selingerová ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Therapy ◽

Retrospective Analysis ◽

Cancer Patients ◽

Germline Mutations ◽

Breast Cancer Patients ◽

Brca1 And Brca2

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Patterns and Prevalence of Germline BRCA1 and BRCA2 Mutations among High-Risk Breast Cancer Patients in Jordan: A Study of 500 Patients

Journal of Oncology ◽

10.1155/2020/8362179 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Hikmat Abdel-Razeq ◽

Lama Abujamous ◽

Dima Jadaan

Keyword(s):

Breast Cancer ◽

High Risk ◽

Cancer Patients ◽

Triple Negative ◽

Positive Family History ◽

Breast Cancer Patients ◽

Brca1 And Brca2 ◽

Variant Of Uncertain Significance ◽

History Of ◽

Close Relatives

Purpose. Knowledge of BRCA1 and BRCA2 mutations has a significant clinical impact on the management and prevention of breast cancer. In this study, we evaluate the pattern and prevalence of germline mutations in BRCA1 and BRCA2 among high-risk Jordanian breast cancer patients selected as per international guidelines. Methods. BRCA1 and BRCA2 testing were performed at a reference genetic lab. Mutations were classified as pathogenic/likely pathogenic and variant of uncertain significance (VUS). Results. A total of 517 patients, median age: 39 (range: 19–78) years, were enrolled. Among the whole group, 72 (13.9%) patients had pathogenic or likely pathogenic BRCA1 (n = 24, 4.6%) or BRCA2 (n = 48, 9.3%) mutations, while 53 (10.3%) others had VUS. Among 333 younger (≤40 years) patients, mutations were observed in 44 (13.2%). Positive mutations were found in 40 (16.5%) patients with one or more close relatives with breast cancer and in 20 (35.1%) of the 57 patients with triple-negative disease. Multivariate analysis showed that a triple-negative status, history of two or more close relatives with breast cancer, and history of one or more close relatives with invasive ovarian cancer were associated with significant high odds ratios (OR) of carrying a pathogenic variant, with an OR (95% CI) of 5.08 (2.66–9.67), 3.24 (1.78–5.89), and 2.97 (1.04–8.52), respectively. Conclusions. BRCA1 and BRCA2 mutations are not uncommon among Jordanian patients. Young age has the weakest association with positive mutations, while patients with triple-negative disease, especially those with an additional positive family history, have the highest mutation rate.

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