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Abstract：
UNASSIGNED: 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).
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
未经证实：应常规对乳腺癌高危患者进行基因检测。产生的知识可能会影响患者自身及其亲属之间的治疗决策和癌症预防策略。在这项研究中,我们报告了生殖系突变的患病率和模式，使用市售的基于下一代测序（NGS）的多基因面板（MGP）。
未经评估：连续有风险的乳腺癌患者，根据国际准则确定，在参考实验室使用基于20个基因NGS的小组提供了种系遗传测试。获得外周血样本进行DNA提取，遗传变异分为良性/可能良性（阴性），致病性/可能致病性（阳性）或意义不确定的变异（VUS）。
未经批准：共有1310名患者，中位年龄（范围）43（19-82）岁，已注册。年龄≤45岁（n=800，61.1％）是最常见的测试指征。乳腺家族史阳性,卵巢,胰腺癌或前列腺癌，和三阴性疾病是常见的适应症。在整个团队中，184例（14.0%）患者有致病性/可能的致病性变异；BRCA1或BRCA2中只有90例（48.9%），而其他94例（51.9%）患者有其他基因的致病性变异；主要在APC中，TP53、CHEK2和PALB2。在有阳性家族史的患者中，突变率明显更高（p=0.009）；特别是如果他们在乳腺癌诊断时50岁或更年轻（p<0.001）。三阴性患者的发病率相对较高（17.5%），且多在BRCA1/2基因(71.4%)。在559例（42.7％）患者中报告了不确定显著性变异（VUS）；大多数（90.7％）在BRCA1或BRCA2以外的基因中。
未经证实：BRCA1/2以外的基因中的致病性突变相对常见，如果基因检测仅限于BRCA1/2，则可能会被漏掉。与多基因小组测试相关的VUS的显着高比率可能令人不安。
未经评估：连续有风险的乳腺癌患者，根据国际准则确定，在参考实验室使用基于20个基因NGS的小组提供了种系遗传测试。获得外周血样本进行DNA提取，遗传变异分为良性/可能良性（阴性），致病性/可能致病性（阳性）或意义不确定的变异（VUS）。
未经批准：共有1310名患者，中位年龄（范围）43（19-82）岁，已注册。年龄≤45岁（n=800，61.1％）是最常见的测试指征。乳腺家族史阳性,卵巢,胰腺癌或前列腺癌，和三阴性疾病是常见的适应症。在整个团队中，184例（14.0%）患者有致病性/可能的致病性变异；BRCA1或BRCA2中只有90例（48.9%），而其他94例（51.9%）患者有其他基因的致病性变异；主要在APC中，TP53、CHEK2和PALB2。在有阳性家族史的患者中，突变率明显更高（p=0.009）；特别是如果他们在乳腺癌诊断时50岁或更年轻（p<0.001）。三阴性患者的发病率相对较高（17.5%），且多在BRCA1/2基因(71.4%)。在559例（42.7％）患者中报告了不确定显著性变异（VUS）；大多数（90.7％）在BRCA1或BRCA2以外的基因中。
未经证实：BRCA1/2以外的基因中的致病性突变相对常见，如果基因检测仅限于BRCA1/2，则可能会被漏掉。与多基因小组测试相关的VUS的显着高比率可能令人不安。
