BRCA2 germline mutations among early onset breast cancer patients unselected for family history of the disease

Abstract Background Germline TP53 mutations are associated with Li-Fraumeni syndrome, a severe and rare hereditary cancer syndrome. Despite the rarity of germline TP53 mutations, the clinical implication for mutation carriers and their families is significant. The risk management of TP53 germline mutation carriers is more stringent than BRCA carriers, and radiotherapy should be avoided when possible. Methods TP53 gene mutation screening was performed in 2538 Chinese breast cancer patients who tested negative for BRCA mutations. Results Twenty TP53 mutations were identified with high next-generation sequencing concerning for germline mutations in Chinese breast cancer families. The majorities of the TP53 carriers had early-onset, hormone receptor-positive breast cancer, and had strong family history of cancer. Among all, 11 patients carried a germline mutation and 6 of which were likely de novo germline mutations. In addition, 1 case was suspected to be induced by chemotherapy or radiation, as this patient had no significant family history of cancer and aberrant clonal expansion can commonly include TP53 mutations. Furthermore, we have identified one mosaic LFS case. Two novel mutations (c.524_547dup and c.529_546del) were identified in patients with early-onset. Conclusions In view of the high lifetime risk of malignancy, identification of patients with germline TP53 mutations are important for clinicians to aid in accurate risk assessment and offer surveillance for patients and their families.

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Contribution of BRCA1 and BRCA2 germline mutations to early onset breast cancer: a series from north of Morocco

BMC Cancer ◽

10.1186/s12885-020-07352-9 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Joaira Bakkach ◽

Mohamed Mansouri ◽

Touria Derkaoui ◽

Ali Loudiyi ◽

ElMostafa El Fahime ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

Early Onset ◽

Brca2 Gene ◽

Germline Mutations ◽

Genetic Alterations ◽

Early Onset Breast Cancer ◽

Brca1 And Brca2 ◽

Brca Mutations ◽

History Of

Abstract Background To date, the contribution of BRCA1/2 mutations in Moroccan early onset breast cancer patients remains unknown. Here we assess these genetic alterations for the first time in a cohort from North of Morocco. Methods Thirty-three patients diagnosed with breast cancer at the age of ≤40 years were recruited irrespective of breast and/or ovarian cancer family history. Coding regions and intron-exon boundaries of BRCA1 and BRCA2 genes were sequenced from peripheral blood DNA using Ion Proton (Thermo Fisher Scientific) next generation sequencing platform. Results Overall, five BRCA germline mutations were identified (15.1%). The frequency of mutations among patients with family history of breast cancer was 16.7%. Three mutations were found in BRCA1 (9%) and two within the BRCA2 gene (6%). These are three frameshift mutations (c.798_799del, c.2125_2126insA, c.5116_5119delAATA), one missense (c.116G > A) and one nonsense mutation (c.289G > T). The mutation c.5116_5119delAATA has a founder effect in North Africa. Moreover, one variant of unknown significance was identified in BRCA2 (c.4090A > G). Most BRCA mutations carriers (80%) had no family history of breast cancer. Conclusion Our data do not support the hypothesis that BRCA mutations alone explain the higher frequency of breast cancer in Moroccan young women. The young age (≤40 years) for breast cancer diagnosis seems to be strongly predictive of BRCA mutation status in Moroccan patients. These results will help in decision making with regard to genetic counseling and testing in the national scale.

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Somatic and germline mutation profiles of Chinese breast cancer patients younger than 35.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.554 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 554-554

Author(s):

Ning Liao ◽

Guo-Chun Zhang ◽

Xiaoqing Chen ◽

Weikai Xiao ◽

Jianguo Lai ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cancer Patients ◽

Germline Mutation ◽

Early Onset ◽

Chinese Women ◽

Germline Mutations ◽

Breast Cancer Patients ◽

Early Onset Breast Cancer ◽

Younger Women

554 Background: Limited studies have investigated the molecular underpinnings driving breast cancer development in Chinese younger women. Based from our previous data, more Chinese women are diagnosed with early-onset breast cancer than in the West. In our study, we aim to investigate the comprehensive mutational profile of Chinese women 35 years old and younger (≤35y) diagnosed with breast cancer. Methods: Targeted sequencing was performed on surgically-removed tumor tissues and blood samples collected from 589 women diagnosed with stage I-III breast cancer of various molecular subtypes at the Guangdong Provincial People’s Hospital (GPDH) using a gene panel interrogating 520 cancer-related genes. We compared the data of 53 women aged ≤35y from our cohort to the data from 33 breast cancer patients aged ≤35y included in The Cancer Genome Atlas (TCGA) dataset. Results: Among the women aged ≤35y with early-stage breast cancer from both cohorts, our cohort had more number of hormone receptor-positive (HR+) patients (GPDH, 72% vs. TCGA, 61%, P< 0.001). Analysis revealed an overall mutation detection rate of 98% in our cohort, with mutations affecting genes involved in the PI3K pathway (47%) and cell cycle pathway (23%). TP53 and PIK3CA were the most commonly mutated genes, with mutation rates of 51% and 25% from our cohort. No statistical difference in mutation profile was found between GPDH and TCGA cohorts. Moreover, germline mutations considered as pathogenic and likely pathogenic (P/LP) in breast cancer susceptibility genes including BRCA1 (n = 4), BRCA2 (n = 2), PALB2 (n = 1), PMS2 (n = 1), PTEN (n = 1), and ATM (n = 1) were detected from 18.9% (10/53) of the patients from our cohort. Women aged ≤35y had significantly more germline BRCA1 mutations than patients > 35y from our cohort (7.5%, 4/53 vs. 2.1%, 11/536 P= 0.049). Conclusions: Our study has identified the involvement of PI3K and cell cycle as the two key pathways in the early development of breast tumors in younger women. In addition, our results also support the role of P/LP germline mutations in breast oncogenesis in Chinese patients with early-onset breast cancer, indicating the need to include a more comprehensive germline mutation screening in our population.

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ATM germline mutations in Spanish early-onset breast cancer patients negative for BRCA1/BRCA2 mutations

Clinical Genetics ◽

10.1111/j.1399-0004.2008.00987.x ◽

2008 ◽

Vol 73 (5) ◽

pp. 465-473 ◽

Cited By ~ 12

Author(s):

J Brunet ◽

S Gutiérrez-Enríquez ◽

A Torres ◽

V Bérez ◽

S Sanjosé ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Early Onset ◽

Germline Mutations ◽

Breast Cancer Patients ◽

Early Onset Breast Cancer ◽

Brca2 Mutations ◽

Brca1 Brca2

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Comparable frequency of BRCA1, BRCA2 and TP53 germline mutations in a multi-ethnic Asian cohort suggests TP53 screening should be offered together with BRCA1/2 screening to early-onset breast cancer patients

Breast Cancer Research ◽

10.1186/bcr3165 ◽

2012 ◽

Vol 14 (2) ◽

pp. R61 ◽

Cited By ~ 5

Author(s):

Daphne SC Lee ◽

Sook-Yee Yoon ◽

Lai Meng Looi ◽

Peter Kang ◽

In Nee Kang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Early Onset ◽

Germline Mutations ◽

Breast Cancer Patients ◽

Early Onset Breast Cancer ◽

Brca1 Brca2 ◽

Asian Cohort ◽

Tp53 Germline Mutations

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New germline mutations in BRCA1, ATM, MUTYH, and RAD51D genes in Tuvans early-onset breast cancer patients

Experimental Oncology ◽

10.32471/exp-oncology.2312-8852.vol-43-no-1.15587 ◽

2021 ◽

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Early Onset ◽

Germline Mutations ◽

Breast Cancer Patients ◽

Early Onset Breast Cancer

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Spectrum and prevalence of BRCA1/2 germline mutations in Pakistani breast cancer patients: results from a large comprehensive study

Hereditary Cancer in Clinical Practice ◽

10.1186/s13053-019-0125-5 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 3

Author(s):

Muhammad Usman Rashid ◽

Noor Muhammad ◽

Humaira Naeemi ◽

Faiz Ali Khan ◽

Mariam Hassan ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Patients ◽

Male Breast Cancer ◽

Early Onset ◽

Germline Mutations ◽

Male Breast ◽

Breast Cancer Patients ◽

Early Onset Breast Cancer ◽

Pakistani Population

Abstract Background Pathogenic germline mutations in BRCA1 and BRCA2 (BRCA1/2) account for the majority of hereditary breast and/or ovarian cancers worldwide. To refine the spectrum of BRCA1/2 mutations and to accurately estimate the prevalence of mutation in the Pakistani population, we studied 539 breast cancer patients selected for family history and age of diagnosis. Methods Comprehensive screening for BRCA1/2 germline mutations was performed using state-of-the-art technologies. Results A total of 133 deleterious mutations were identified in 539 families (24.7%), comprising 110 in BRCA1 and 23 in BRCA2. The prevalence of BRCA1/2 small-range mutations and large genomic rearrangements was 55.4% (36/65) for families with breast and ovarian cancer, 27.4% (67/244) for families with two or more cases of breast cancer, 18.5% (5/27) for families with male breast cancer, and 12.3% (25/203) for families with a single case of early-onset breast cancer. Nine mutations were specific to the Pakistani population. Eighteen mutations in BRCA1 and three in BRCA2 were recurrent and accounted for 68.2% (75/110) and 34.8% (8/23) of all identified mutations in BRCA1 and BRCA2, respectively. Most of these mutations were exclusive to a specific ethnic group and may result from founder effects. Conclusions Our findings show that BRCA1/2 mutations account for one in four cases of hereditary breast/ovarian cancer, one in five cases of male breast cancer, and one in eight cases of early-onset breast cancer in Pakistan. Our study suggests genetic testing of an extended panel of 21 recurrent BRCA1/2 mutations for appropriately selected patients and their families in Pakistan.

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Comparable frequency of BRCA1, BRCA2 and TP53 germline mutations in a multi-ethnic Asian cohort suggests TP53 screening should be offered together with BRCA1/2 screening to early-onset breast cancer patients

Breast Cancer Research ◽

10.1186/bcr3172 ◽

2012 ◽

Vol 14 (2) ◽

Cited By ~ 30

Author(s):

Daphne SC Lee ◽

Sook-Yee Yoon ◽

Lai Meng Looi ◽

Peter Kang ◽

In Nee Kang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Early Onset ◽

Germline Mutations ◽

Breast Cancer Patients ◽

Early Onset Breast Cancer ◽

Brca1 Brca2 ◽

Asian Cohort ◽

Tp53 Germline Mutations

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Evaluating the Effect of Health Education Intervention on the Health Beliefs and Behaviors of First-Degree Female Relatives of Breast Cancer Patients

South Asian Journal of Cancer ◽

10.1055/s-0041-1733318 ◽

2021 ◽

Author(s):

Sule Olgun ◽

Berna Dizer

Keyword(s):

Breast Cancer ◽

Family History ◽

Health Education ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Cancer Patients ◽

Health Beliefs ◽

Breast Cancer Patients ◽

History Of ◽

And Behaviors

Abstract Background Breast cancer risk increases by 80% in the presence of BRCA1 and BRCA2 gene mutations in the same family. In particular, a woman whose sister or mother has breast cancer has a 2- to 5-fold higher risk of developing breast cancer compared with other women. For this reason, recommendations should have been made regarding breast cancer prevention and/or early detection for women with first-degree family history of breast cancer. Aim The aim of this study was to evaluate the effect of health education, which was provided to first-degree female relatives of breast cancer patients, on their health beliefs and behaviors. Study Design and Methods The study sample included 50 women with a first-degree relative being treated for breast cancer in the chemotherapy and radiotherapy unit of a university hospital. A one-group pretest-posttest design was used. The pretest consisted of the health belief model scale and a questionnaire regarding the women’s sociodemographic information and breast cancer screening behaviors. After the pretest, the patients received health education regarding breast cancer risk factors and screening methods. The posttest was conducted 3 weeks after the education using the same assessment tools. Results After education, there were statistically significant increases in rates of practicing breast self-examination, having clinical breast examinations, and undergoing breast ultrasound/mammography compared with pretest results. Conclusions Health workers should possess knowledge and experience about breast cancer which will enable them to effectively undertake an educational role, especially for high-risk groups such as women with first-degree family history of breast cancer.

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