ATM、CHEK2和PALB2这三种最常见的中度风险乳腺癌基因对手术决策的影响尚不清楚。我们的回顾性研究纳入了在2014年7月至2020年1月期间接受多基因面板测试的可切除非转移性乳腺癌患者，其中至少有一种ATM（n = 49）、CHEK（n = 57）或PALB2（n = 27）的遗传变异（有病原性或不确定意义[VoUS]）。我们的目标是确定对侧预防性乳房切除术（CPM）和双侧乳腺癌发生率。采用单变量分析（UVA）和多变量分析（MVA）来确定与CPM和双侧乳腺癌相关的因素。CPM的发生率为39%（n = 49/127），其中54%（n = 25/46）的患者携带有致病变异，30%（n = 24/81）的患者携带VoUS选择进行了CPM。在MVA中，绝经前状态（OR 3.46）和致病变异（OR 3.01）与CPM的使用增加相关。双侧乳腺癌发生率为16%（n = 22/138）。带有致病变异的患者双侧乳腺癌发生率为22%（n = 11/51），而VoUS的患者为13%（n = 11/87），尽管在UVA和MVA上没有统计学意义。在MVA中，绝经前状态与双侧乳腺疾病的风险降低相关（OR 0.33，p = 0.022）。在随访期间，有16%（n = 22/138）的患者发生乳腺癌事件。我们的研究发现，携带ATM、CHEK2和PALB2变异的患者，包括VoUS变异，CPM的发生率很高。进一步的研究需要澄清针对中度风险变异患者选择CPM的原因。© 2023年外科肿瘤学会。

The impact of ATM, CHEK2, and PALB2, the three most prevalent moderate-risk breast cancer genes, on surgical decision making is not well known.Our retrospective study included patients with resectable non-metastatic breast cancer who underwent multigene panel testing between July 2014 and January 2020 with at least one genetic alteration (pathogenic or variant of uncertain significance [VUS] in ATM [n = 49], CHEK [n = 57], or PALB2 [n = 27]). Our objectives were to determine the rate of contralateral prophylactic mastectomy (CPM) and the rate of bilateral breast cancer. Univariable analyses (UVA) and multivariable analyses (MVA) were performed to identify factors associated with CPM and bilateral breast cancer.The rate of CPM was 39% (n = 49/127), with 54% (n = 25/46) of patients with a pathogenic mutation and 30% (n = 24/81) of patients with a VUS choosing CPM. On MVA, premenopausal status (odds ratio [OR] 3.46) and a pathogenic alteration (OR 3.01) were associated with increased use of CPM. Bilateral disease was noted in 16% (n = 22/138). Patients with pathogenic mutations had a 22% (n = 11/51) incidence of bilateral breast cancer, while patients with VUS had a 13% (n = 11/87) incidence, although this was not statistically significant on UVA or MVA. On MVA, premenopausal status was associated with a decreased risk of bilateral disease (OR 0.33, p = 0.022). During follow-up, a breast cancer event occurred in 16% (n = 22/138).Our study identified a high rate of CPM among those with ATM, CHEK2, and PALB2 alterations, including VUS. Further studies are needed to clarify reasons for CPM among patients with moderate-risk alterations.© 2023. Society of Surgical Oncology.