Prevalence and predictors of germline BRCA1 and BRCA2 mutations among young patients with breast cancer in Jordan

Abstract

BRCA1 and BRCA2 mutations are not uncommon in breast cancer patients. Western studies show that such mutations are more prevalent among younger patients. This study evaluates the prevalence of germline mutations in BRCA1 and BRCA2 among breast cancer patients diagnosed at age 40 or younger in Jordan. Blood samples of patients with breast cancer diagnosed at age 40 years or younger were obtained for DNA extraction and BRCA sequencing. Mutations were classified as benign/likely benign (non-carrier), pathogenic/likely pathogenic variant (carrier) and variant of uncertain significance (VUS). Genetic testing and counseling were completed on 616 eligible patients. Among the whole group, 75 (12.2%) had pathogenic or likely pathogenic variants; two of the BRCA2 mutations were novel. In multivariate analysis, triple-negative disease (Odd Ratio [OR]: 5.37; 95% CI 2.88–10.02, P < 0.0001), breast cancer in ≥ 2 family members (OR: 4.44; 95% CI 2.52–7.84, P < 0.0001), and a personal history ≥ 2 primary breast cancers (OR: 3.43; 95% CI 1.62–7.24, P = 0.001) were associated with higher mutation rates. In conclusion, among young Jordanian patients with breast cancer, mutation rates are significantly higher in patients with triple-negative disease, personal history of breast cancer and those with two or more close relatives with breast cancer.

Breast cancer in West Africa: molecular analysis of BRCA genes in early-onset breast cancer patients in Burkina Faso

“…In BRCA2 gene, we identified three pathogenic variants, two frameshift mutations and one missense mutation, in three unrelated patients. The frameshift variant c.6445_6446del, (p.Ile2149*) [ 18 ] was identified in a patient with breast ductal carcinoma, diagnosed at age of 37 and no family history of breast cancer; the frameshift variant c.6757_6758del, (p.Leu2253Phefs*7) [ 15 ] was identified in a patient with breast ductal carcinoma, diagnosed at age of 37 and with a family history of breast cancer. The missense mutation, c.8009C>T, (p. Ser2670Leu) [ 19 ], was present in a 37-years-old woman with a medullary breast carcinoma and a family history for breast cancer.…”

Latency of breast cancer stigma during survivorship and its influencing factors: A qualitative study

“…“Origin” refers to whether patients are thought to be responsible for their cancer (e.g., smoking, obesity, poor diet, or lifestyle). Because breast cancer is sometimes thought to be hereditary (due to genetic susceptibility (e.g., BRACA1/2 germline and family history)) ( 3 ), having a family member with cancer makes people feel as if their feeling of security is jeopardised or that they are not immune to cancer.…”

“…The median age at presentation is 52 years, ten years younger than the median age in developed countries. Additionally, about a third of patients present with locally advanced or metastatic disease, highlighting the critical nature of early detection programmes ( 3 ).…”

Identification of a TP53 Mutation in a Patient With Li-Fraumeni Syndrome and Not Meeting the Revised Chompret Criteria: A Case Report

“…Thus, negative BRCA1/2 results alone may not necessarily lead to the decision to conduct TP53 genetic testing. In contrast, HER2 positivity is present in 19% of breast cancer patients below the age of 49 years in the U.S., which may create a dilemma regarding whether to conduct genetic testing for all HER2-positive patients [ 8 ]. Although we were able to conduct genetic testing for TP53 due to the history of multiple cancers, our case highlights the importance of considering genetic testing for TP53 even if the revised Chompret and classic LFS diagnostic criteria are not satisfied.…”