Screening, Risk Reduction Strategies, and Clinical Management of Unaffected Carriers of BRCA1 or BRCA2 Pathogenic Variants

Sep 28, 2026

Uploaded by Mary Man

Breast cancer remains the most common cancer globally, with approximately 5-15% of cases linked to pathogenic variants primarily in BRCA1 or BRCA2. These mutations markedly increase cancer risk, creating a need for effective screening and prevention for unaffected carriers. This narrative review summarizes evidence and proposes a comprehensive risk-reduction approach, covering surveillance, enhanced imaging, risk-reducing surgeries, and chemoprevention, while addressing barriers to uptake and psychological impacts.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Introduction

Screening and risk-reduction strategies

Surveillance and enhanced imaging

Chemoprevention with SERMs and aromatase inhibitors

Risk-reducing surgeries

Barriers to uptake and psychological impact

Role of family communication and supportive counseling

Review World J Oncol. 2026;17(1):14-24 Screening, Risk Reduction Strategies, and Clinical Management of Unaffected Carriers of BRCA1 or BRCA2 Pathogenic Variants Hikmat Abdel-Razeqa, b, d, Razan Mansourc Abstract Breast cancer remains the most common cancer globally, with approximately 5-15% of cases linked to pathogenic variants primarily in BRCA1 or BRCA2 . These mutations greatly increase cancer risks, highlighting the critical need for more effective screening and prevention strategies. This review aimed to summarize existing evidence and propose a comprehensive approach to reducing cancer risk in unaffected mutation carriers. A narrative review of published literature was conducted to evaluate risk-reduction strategies, including surveillance, enhanced imaging, risk-reducing surgeries, and chemoprevention. Barriers to the uptake of these strategies and the psychological impact on carriers were also examined. Annual magnetic resonance imaging (MRI) remains the most sensitive screening tool for early breast cancer detection in highrisk individuals. Selective estrogen receptor modulators (SERMs) and aromatase inhibitors have shown potential as chemopreventive agents, but uptake remains limited due to concerns about efficacy and side effects. Risk-reducing surgeries, such as bilateral salpingooophorectomy (BSO) and mastectomy, significantly lower the risk of breast and ovarian cancer; however, their uptake is often hindered by emotional, cultural, and financial factors. Family communication of genetic results and support by healthcare professionals are critical to encouraging preventive actions. Effective screening and risk-reduction strategies are available for BRCA1 and BRCA2 carriers, yet barriers to implementation persist. Personalized counseling, enhanced accessibility, and culturally sensitive education are essential to improving the adoption of these preventive measures. Further studies are needed to explore novel chemoprevention options and interventions to address the unmet needs of carriers worldwide. Manuscript submitted October 15, 2025, accepted December 1, 2025 Published online December 17, 2025 aDepartment of Internal Medicine, King Hussein Cancer Center, Amman 11941, Jordan bSchool of Medicine, University of Jordan, Amman 11942, Jordan cDepartment of Hematology/Oncology, Yale School of Medicine, New Haven, CT 06510, USA dCorresponding Author: Hikmat Abdel-Razeq, Section of Hematology and Medical Oncology, Department of Internal Medicine, King Hussein Cancer Center, PO Box 1269, Amman 11941, [Jordan. Email: habdelrazeq@khcc.jo](Jordan. Email: habdelrazeq@khcc.jo) doi: [https://doi.org/10.14740/wjon2692](https://doi.org/10.14740/wjon2692) Keywords: BRCA1; BRCA2; Germline genetic testing; Carrier; Riskreducing surgery; Prophylactic mastectomy; Oophorectomy; BSO Introduction Breast cancer remains the most frequently diagnosed malignancy in women worldwide. In 2022, almost 2.3 million cases were diagnosed, with an estimated death toll of over 666,000 [1, 2] . In 2024, approximately 311,000 new cases of invasive breast cancer and 56,500 cases of ductal carcinoma in situ (DCIS) will be diagnosed among US women, and 42,250 women will die from breast cancer, highlighting the importance of effective and more accessible breast cancer screening and risk-reduction strategies [3] . Lifetime risk for breast cancer varies across countries due to differences in population structure, screening practices, and access to healthcare systems. In the United States, it is estimated that one in eight women will develop breast cancer in their lifetime [3] . Over the past decade, knowledge and experience have helped identify a subgroup of women at higher risk than others. Age, reproductive background, and a family history of breast and ovarian cancer are recognized contributors to risk. Additionally, prior breast biopsies, especially those with findings like atypical hyperplasia (AH), or lobular carcinoma in sit

FAQs

What is the purpose of the review for BRCA1/BRCA2 unaffected carriers?

To summarize existing evidence and propose a comprehensive approach to reducing cancer risk in unaffected mutation carriers, including screening, prevention, and supportive strategies.

Which screening method is described as the most sensitive for early breast cancer detection?

Annual magnetic resonance imaging (MRI) is described as the most sensitive screening tool for early breast cancer detection in high-risk individuals.

Why is uptake of chemoprevention strategies limited?

Uptake is limited due to concerns about efficacy and side effects, despite evidence that SERMs and aromatase inhibitors may help prevent cancer.

Sep 28, 2026

Uploaded by Mary Man