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Abstract：
BACKGROUND: The impact of ATM, CHEK2, and PALB2, the three most prevalent moderate-risk breast cancer genes, on surgical decision making is not well known.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
摘要：
背景：ATM的影响，CHEK2和PALB2是三种最普遍的中度风险乳腺癌基因，关于外科手术的决策并不为人所知。
方法：我们的回顾性研究包括在2014年7月至2020年1月期间接受多基因组检测的可切除非转移性乳腺癌患者，这些患者至少有一种遗传改变（ATM中致病性或意义不确定的变异[VUS][n=49]，CHEK[n=57],或PALB2[n=27])。我们的目标是确定对侧预防性乳房切除术（CPM）的发生率和双侧乳腺癌的发生率。进行单变量分析（UVA）和多变量分析（MVA）以确定与CPM和双侧乳腺癌相关的因素。
结果：CPM率为39％（n=49/127），54％（n=25/46）的致病性突变患者和30％（n=24/81）的VUS患者选择CPM。在MVA上，绝经前状态(比值比[OR]3.46)和致病改变(OR3.01)与CPM使用增加相关.双侧疾病占16％（n=22/138）。有致病突变的患者有22%(n=11/51)的双侧乳腺癌发病率,而VUS患者的发病率为13%(n=11/87)，尽管这在UVA或MVA上没有统计学意义。在MVA上，绝经前状态与双侧疾病风险降低相关(OR0.33,p=0.022).随访期间,16%的患者发生了乳腺癌事件(n=22/138).
结论：我们的研究发现，在ATM患者中，CPM的发生率很高，CHEK2和PALB2改变，包括VUS。需要进一步的研究来阐明中度风险改变患者CPM的原因。
方法：我们的回顾性研究包括在2014年7月至2020年1月期间接受多基因组检测的可切除非转移性乳腺癌患者，这些患者至少有一种遗传改变（ATM中致病性或意义不确定的变异[VUS][n=49]，CHEK[n=57],或PALB2[n=27])。我们的目标是确定对侧预防性乳房切除术（CPM）的发生率和双侧乳腺癌的发生率。进行单变量分析（UVA）和多变量分析（MVA）以确定与CPM和双侧乳腺癌相关的因素。
结果：CPM率为39％（n=49/127），54％（n=25/46）的致病性突变患者和30％（n=24/81）的VUS患者选择CPM。在MVA上，绝经前状态(比值比[OR]3.46)和致病改变(OR3.01)与CPM使用增加相关.双侧疾病占16％（n=22/138）。有致病突变的患者有22%(n=11/51)的双侧乳腺癌发病率,而VUS患者的发病率为13%(n=11/87)，尽管这在UVA或MVA上没有统计学意义。在MVA上，绝经前状态与双侧疾病风险降低相关(OR0.33,p=0.022).随访期间,16%的患者发生了乳腺癌事件(n=22/138).
结论：我们的研究发现，在ATM患者中，CPM的发生率很高，CHEK2和PALB2改变，包括VUS。需要进一步的研究来阐明中度风险改变患者CPM的原因。
