Abstract：
BACKGROUND: Management of pathogenic variants in high penetrance genes related to breast cancer (BC), such as BRCA1 and BRCA2, are well established. However, moderate penetrance mutations are understudied. We aim to compare risk reduction decision-making patterns in patients with a moderate penetrance BC-related genetic mutations, without a prior BC diagnosis.
METHODS: Female patients aged ≥ 18 years who tested positive for a BRCA1/2, high penetrance, or moderate penetrance mutation related to BC between 1996 and 2023 without a concurrent or prior BC diagnosis were retrospectively identified from a single academic center\'s database. Groups were stratified by mutation type: BRCA1/2 mutations (BRCA1, BRCA2), high penetrance mutations (HPM; CDH1, PALB2, PTEN, STK11, TP53), or moderate penetrance mutations (MPM; ATM, BARD1, CHEK2, NF1, RAD51C, RAD51D). Demographics and clinical outcomes were compared.
RESULTS: A total of 528 patients met the inclusion criteria, with 66% (n = 350) having a BRCA1/2 mutation, 8% (n = 44) having HPM, and 25% (n = 134) having MPM; the median follow-up was 56.0 months. In our cohort, 20.9% of patients with BRCA mutations, 9.1% with HPM, and 7.5% with MPM chose to undergo risk-reducing mastectomies (RRM). Within the moderate penetrance cohort, patients who chose to undergo RRM were younger at the time of genetic testing (39.4 vs. 47.5 years, p = 0.03) and had a higher number of family members with BC (2 vs. 1, p = 0.05).
CONCLUSIONS: Our findings provide insights into the demographic characteristics and family history of patients with moderate penetrance mutations and those who pursue risk-reducing surgery.
METHODS: Female patients aged ≥ 18 years who tested positive for a BRCA1/2, high penetrance, or moderate penetrance mutation related to BC between 1996 and 2023 without a concurrent or prior BC diagnosis were retrospectively identified from a single academic center\'s database. Groups were stratified by mutation type: BRCA1/2 mutations (BRCA1, BRCA2), high penetrance mutations (HPM; CDH1, PALB2, PTEN, STK11, TP53), or moderate penetrance mutations (MPM; ATM, BARD1, CHEK2, NF1, RAD51C, RAD51D). Demographics and clinical outcomes were compared.
RESULTS: A total of 528 patients met the inclusion criteria, with 66% (n = 350) having a BRCA1/2 mutation, 8% (n = 44) having HPM, and 25% (n = 134) having MPM; the median follow-up was 56.0 months. In our cohort, 20.9% of patients with BRCA mutations, 9.1% with HPM, and 7.5% with MPM chose to undergo risk-reducing mastectomies (RRM). Within the moderate penetrance cohort, patients who chose to undergo RRM were younger at the time of genetic testing (39.4 vs. 47.5 years, p = 0.03) and had a higher number of family members with BC (2 vs. 1, p = 0.05).
CONCLUSIONS: Our findings provide insights into the demographic characteristics and family history of patients with moderate penetrance mutations and those who pursue risk-reducing surgery.
摘要：
背景：与乳腺癌（BC）相关的高外显率基因的致病变异的管理，如BRCA1和BRCA2，是公认的。然而,中度外显率突变研究不足。我们旨在比较中度外显率BC相关基因突变患者的风险降低决策模式。没有先前的BC诊断。
方法：年龄≥18岁、BRCA1/2、高外显率、我们从一个学术中心的数据库中回顾性鉴定了1996年至2023年间与BC相关的或中度外显突变,但没有同时或先前的BC诊断.组按突变类型分层：BRCA1/2突变（BRCA1，BRCA2），高外显率突变(HPM；CDH1，PALB2，PTEN，STK11,TP53),或中度外显率突变(MPM；ATM，BARD1,CHEK2,NF1,RAD51C,RAD51D)。比较人口统计学和临床结果。
结果：共528例患者符合纳入标准，66%（n=350）有BRCA1/2突变，8%(n=44)有HPM，25％（n=134）患有MPM；中位随访时间为56.0个月。在我们的队列中，20.9%的BRCA突变患者，9.1%的HPM，7.5%的MPM患者选择接受降低风险的乳腺切除术(RRM)。在中等外显率队列中，选择接受RRM的患者在基因检测时更年轻(39.4vs.47.5年,p=0.03），并且BC的家庭成员数量较多（2vs.1,p=0.05)。
结论：我们的研究结果为中度外显突变患者和进行降低风险手术患者的人口统计学特征和家族史提供了见解。
方法：年龄≥18岁、BRCA1/2、高外显率、我们从一个学术中心的数据库中回顾性鉴定了1996年至2023年间与BC相关的或中度外显突变,但没有同时或先前的BC诊断.组按突变类型分层：BRCA1/2突变（BRCA1，BRCA2），高外显率突变(HPM；CDH1，PALB2，PTEN，STK11,TP53),或中度外显率突变(MPM；ATM，BARD1,CHEK2,NF1,RAD51C,RAD51D)。比较人口统计学和临床结果。
结果：共528例患者符合纳入标准，66%（n=350）有BRCA1/2突变，8%(n=44)有HPM，25％（n=134）患有MPM；中位随访时间为56.0个月。在我们的队列中，20.9%的BRCA突变患者，9.1%的HPM，7.5%的MPM患者选择接受降低风险的乳腺切除术(RRM)。在中等外显率队列中，选择接受RRM的患者在基因检测时更年轻(39.4vs.47.5年,p=0.03），并且BC的家庭成员数量较多（2vs.1,p=0.05)。
结论：我们的研究结果为中度外显突变患者和进行降低风险手术患者的人口统计学特征和家族史提供了见解。
