Management Strategies of Breast Cancer Patients with BRCA1 and BRCA2 Pathogenic Germline Variants

Edaily, Sarah; Abdel‐Razeq, Hikmat

doi:10.2147/ott.s369844

Cited by 6 publications

(4 citation statements)

References 81 publications

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“…In addition to breast and ovarian cancer prevention, the utilization of our knowledge about mutations in BRCA1 and BRCA2 , and even in non- BRCA mutations, in treatment decisions is increasing. 30 Patients with TN-breast cancer and deleterious BRCA1/2 mutations have better response rate and progression-free survival (PFS) when treated with carboplatin compared to docetaxel. 31 PARP (poly (ADP)-ribose polymerase) inhibitors were also tried in patients with pathogenic BRCA1/2 advanced-stage breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Guideline-Based, Multi-Gene Panel Germline Genetic Testing for at-Risk Patients with Breast Cancer

Abdel‐Razeq¹,

Abujamous²,

Al-Azzam³

et al. 2023

BCTT

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Background Genetic testing for at-risk patients with breast cancer should be routinely offered. Knowledge generated may influence both treatment decisions and cancer prevention strategies among the patients themselves and their relatives. In this study, we report on the prevalence and patterns of germline mutations, using commercially available next-generation sequencing (NGS)-based multi-gene panels (MGP). Patients and Methods Consecutive at-risk breast cancer patients, as determined by international guidelines, were offered germline genetic testing using a 20-gene NGS-based panel at a reference lab. Samples of peripheral blood were obtained for DNA extraction and genetic variants were classified as benign/likely benign (negative), pathogenic/likely pathogenic (positive) or variants of uncertain significance (VUS). Results A total of 1310 patients, median age (range) 43 (19–82) years, were enrolled. Age ≤45 years (n = 800, 61.1%) was the most common indication for testing. Positive family history of breast, ovarian, pancreatic or prostate cancers, and triple-negative disease were among the common indications. Among the whole group, 184 (14.0%) patients had pathogenic/likely pathogenic variants; only 90 (48.9%) were in BRCA1 or BRCA2 , while 94 (51.9%) others had pathogenic variants in other genes; mostly in APC, TP53, CHEK2 and PALB2 . Mutation rates were significantly higher among patients with positive family history (p = 0.009); especially if they were 50 years or younger at the time of breast cancer diagnosis (p < 0.001). Patients with triple-negative disease had relatively higher rate (17.5%), and mostly in BRCA1/2 genes (71.4%). Variants of uncertain significance (VUS) were reported in 559 (42.7%) patients; majority (90.7%) were in genes other than BRCA1 or BRCA2 . Conclusion Pathogenic mutations in genes other than BRCA1/2 are relatively common and could have been missed if genetic testing was restricted to BRCA1/2 . The significantly high rate of VUS associated with multi-gene panel testing can be disturbing.

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Section: Discussionmentioning

confidence: 99%

Guideline-Based, Multi-Gene Panel Germline Genetic Testing for at-Risk Patients with Breast Cancer

Abdel‐Razeq¹,

Abujamous²,

Al-Azzam³

et al. 2023

BCTT

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“…As patients with BRCA mutations present significantly higher risk for breast cancer development, enhanced surveillance methods and proper genetic counselling are necessary. Prophylactic measures may include double mastectomy and oophorectomy [23,24].…”

Section: Genetic Risk Factors In Breast Cancermentioning

confidence: 99%

Breast Cancer Screening and Prophylactic Mastectomy for High-Risk Women in Romania

Filip,

Cătană,

Kutasi

et al. 2024

Medicina

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Breast cancer remains a significant contributor to morbidity and mortality within oncology. Risk factors, encompassing genetic and environmental influences, significantly contribute to its prevalence. While germline mutations, notably within the BRCA genes, are commonly associated with heightened breast cancer risk, a spectrum of other variants exists among affected individuals. Diagnosis relies on imaging techniques, biopsies, biomarkers, and genetic testing, facilitating personalised risk assessment through specific scoring systems. Breast cancer screening programs employing mammography and other imaging modalities play a crucial role in early detection and management, leading to improved outcomes for affected individuals. Regular screening enables the identification of suspicious lesions or abnormalities at earlier stages, facilitating timely intervention and potentially reducing mortality rates associated with breast cancer. Genetic mutations guide screening protocols, prophylactic interventions, treatment modalities, and patient prognosis. Prophylactic measures encompass a range of interventions, including chemoprevention, hormonal inhibition, oophorectomy, and mastectomy. Despite their efficacy in mitigating breast cancer incidence, these interventions carry potential side effects and psychological implications, necessitating comprehensive counselling tailored to individual cases.

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“…Almost one in five patients with newly diagnosed breast cancer report a family history of breast cancer (3)(4)(5). However, smaller fraction may be attributed to an inherited cancer-predisposing gene, mostly in BRCA1 or BRCA2 (6). Based on one meta-analysis, the estimated mean cumulative risk for developing breast cancer by age 70 for carriers of the BRCA1 variant is 57%, whereas the risk for carriers of the BRCA2 variant is a little lower at 49% (7).…”

Section: Introductionmentioning

confidence: 99%

Surgical options for patients with early-stage breast cancer and pathogenic germline variants: an oncologist perspectives

Abdel-Razeq

2023

Front. Oncol.

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Breast cancer continues to be the most common cancer diagnosed among women worldwide. Family history of breast cancer is frequently encountered, and 5-15% of patients may carry inherited pathogenic germline variants, identification of which can be helpful for both; patients themselves and their unaffected close relatives. The availability and affordability of molecular diagnostics, like next generation sequencing (NGS), had resulted in wider adoption of such technologies to detect pathogenic variants of cancer-predisposing genes. International guidelines had recently broadened the indications for germline genetic testing to include much more patients, and also expanded the testing to include multi-gene panels, while some professional societies are calling for universal testing of all newly diagnosed patients with breast cancer, regardless of their age, personal or family history. The risk of experiencing a contralateral breast cancer (CBC) or ipsilateral recurrence, is well known. Such risk is highest with variants like BRCA1 and BRCA2, but less well-studied with other less common variants. The optimal local therapy for women with BRCA-associated breast cancer remains controversial, but tends to be aggressive and may involve bilateral mastectomies, which may not have any survival advantage. Additionally, surgical management of unaffected women, known to carry a pathogenic cancer-predisposing gene, may vary from surveillance to bilateral mastectomies, too. The oncological safety, and the higher satisfaction of unaffected women and patients with new surgical techniques, like the skin-sparing (SSM) and nipple-sparing (NSM) mastectomies, eased up the process of counselling. In this review, we address the oncological safety of less aggressive surgical options for both; patients and unaffected carriers.

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Management Strategies of Breast Cancer Patients with BRCA1 and BRCA2 Pathogenic Germline Variants

Cited by 6 publications

References 81 publications

Guideline-Based, Multi-Gene Panel Germline Genetic Testing for at-Risk Patients with Breast Cancer

Guideline-Based, Multi-Gene Panel Germline Genetic Testing for at-Risk Patients with Breast Cancer

Breast Cancer Screening and Prophylactic Mastectomy for High-Risk Women in Romania

Surgical options for patients with early-stage breast cancer and pathogenic germline variants: an oncologist perspectives

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