Abstract
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.
Highlights
Accounting for almost 20% of all cancer cases, breast cancer continues to be the most common cancer and the leading cause of cancer-related deaths among Jordanian women
In patients with advanced breast cancer associated with BRCA1 or BRCA2 mutations, olaparib and talazoparib are approved for treatment [8,9,10,11]
Patients who consented to BRCA1 and BRCA2 testing were referred to our genetic counseling clinic where a lengthy interview and discussion by a trained genetic counselor were carried out
Summary
Accounting for almost 20% of all cancer cases, breast cancer continues to be the most common cancer and the leading cause of cancer-related deaths among Jordanian women. Almost 50% of breast cancer patients are diagnosed at the age of 50 or younger. Published data had shown that 5–10% of breast cancer is hereditary and mostly related to BRCA1 or BRCA2 gene mutations [4, 5]. Efforts to identify such mutations are extremely important given the high penetrance rates among its carriers [6]. Data had shown that specific breast cancer treatment may be informed by the BRCA1 or BRCA2 mutation status. In patients with advanced breast cancer associated with BRCA1 or BRCA2 mutations, olaparib and talazoparib are approved for treatment [8,9,10,11]
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