Abdel-Razeq Hikmat, Tamimi Faris, Abujamous Lama, Abdel-Razeq Rashid, Abunasser Mahmoud, Edaily Sara, Abdulelah Hazem, Khashabeh Razan Abu, Bater Rayan
Department of Medicine, King Hussein Cancer Center, Amman, Jordan.
School of Medicine, University of Jordan, Amman, Jordan.
Front Oncol. 2022 Mar 25;12:673094. doi: 10.3389/fonc.2022.673094. eCollection 2022.
Contrary to BRCA pathogenic variants, recommendations for management of variants of uncertain significance (VUS) are not clear and focus more on the patient's family and personal history of cancer. Local and regional data on VUS are scarce. In this paper, we study patterns and frequency of VUS among breast cancer patients undergoing genetic testing.
Patients with breast cancer at high risk for pathogenic variants, as per the National Comprehensive Cancer Network (NCCN) guidelines, were tested at reference laboratories. Related surgical interventions were reviewed.
Among a group of 1,197 patients with breast cancer who underwent genetic testing and counseling, 110 (9.2%) had VUS; most (n = 79, 71.8%) were in . Median age (range) was 39 (25-66) years with 65 (59.1%) patients who were 40 years or younger at diagnosis. Among 103 patients with non-metastatic disease, 48 (46.6%) had breast-conserving surgery (BCS) while only 5 (4.9%) had bilateral mastectomies; all were due to bilateral disease and not prophylactic. VUS diagnosis was known prior to initial surgery in 34 (33.0%) patients; 11 (32.4%) of them had BCS only. Over the study period, only one VUS variant was upgraded to "likely positive." The recent introduction of multiple-gene panel testing had resulted in a surge in VUS rate (22.2%) in genes other than or , like , and
Rates of VUS are relatively high and increasing, mostly in non- or , and this had no impact on the therapeutic or prophylactic surgical decisions. Adherence to guidelines is extremely important to avoid unnecessary procedures.
与BRCA致病变异不同，意义未明变异（VUS）的管理建议并不明确，更多地侧重于患者的家族和个人癌症病史。关于VUS的局部和区域数据稀缺。在本文中，我们研究了接受基因检测的乳腺癌患者中VUS的模式和频率。
根据美国国立综合癌症网络（NCCN）指南，对有致病变异高风险的乳腺癌患者在参考实验室进行检测。回顾相关手术干预措施。
在一组接受基因检测和咨询的1197例乳腺癌患者中，110例（9.2%）有VUS；大多数（n = 79，71.8%）位于 。中位年龄（范围）为39（25 - 66）岁，65例（59.1%）患者诊断时年龄在40岁及以下。在103例非转移性疾病患者中，48例（46.6%）接受了保乳手术（BCS），而只有5例（4.9%）进行了双侧乳房切除术；所有这些均因双侧疾病而非预防性目的。34例（33.0%）患者在初次手术前已知VUS诊断；其中11例（32.4%）仅接受了BCS。在研究期间，只有一个VUS变异被升级为“可能阳性”。近期多基因检测面板的引入导致除 或 之外的基因（如 、 ）中VUS率激增（22.2%）。
VUS发生率相对较高且呈上升趋势，主要存在于非 或 基因中，这对治疗或预防性手术决策没有影响。遵循指南对于避免不必要的手术极为重要。
