ATM Variants in Breast Cancer: Implications for Breast Radiation Therapy Treatment Recommendations
ATM Variants in Breast Cancer: Implications for Breast Radiation Therapy Treatment Recommendations
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DOI：
10.1016/j.ijrobp.2021.01.045
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发表时间：
2021-07-14
影响因子：
7
通讯作者：
Ho, Alice Y.
中科院分区：
文献类型：
--
作者：
McDuff, Susan G. R.;Bellon, Jennifer R.;Ho, Alice Y.
目的：种系基因检测的进步导致乳腺癌患者中共济失调毛细血管扩张突变 (ATM) 变异携带者的鉴定激增，引发了有关在该人群中使用乳房放射治疗 (RT) 的许多问题。方法：使用 PubMed 进行文献检索，找到了评估种系 ATM 变异状态与乳房 RT 后毒性风险之间关联的文章。由乳腺放射肿瘤学家、遗传咨询师和基础科学家组成的专家小组召开会议，审查 ATM 变异与辐射引起的毒性或继发性恶性肿瘤风险之间的关联，并确定对乳房 RT 建议的影响。结果：ATM 致病变异携带者患乳腺癌的风险增加 2 至 4 倍。 ATM 变体并不总是增加放疗后毒性的风险，但可能在具有单核苷酸变体 c5557G>A (rs1801516) 的患者中除外，在这些患者中，已发现发生急性和晚期放射效应的风险略有增加。在大多数携带 ATM 变异的乳腺癌患者中，放疗后 5 年发生继发性对侧乳腺癌 (CBC) 的绝对风险极低。例外情况是年龄小于 45 岁、患有有害的罕见 ATM 错义变异的女性，随着时间的推移，她们发生放射诱发的 CBC 的风险可能更高。结论：辅助放射对于大多数携带 ATM 变异的乳腺癌患者是安全的。可能的例外是携带 c5557G>A 变异 (rs1801516) 的患者和年龄小于 45 岁、携带某些罕见有害 ATM 变异的患者，这些患者发生 CBC 的风险可能较高。应告知后者患者这种潜在风险，并应尽一切努力尽量减少对侧乳房的剂量。然而，已发表数据的不一致限制了精确的建议，加大了进一步前瞻性研究和开发记录 RT 结果和遗传状态的集中数据库的需要。 (C) 2021 Elsevier Inc. 保留所有权利。
Purpose: Advances in germline genetic testing have led to a surge in identification of ataxia-telangiectasia mutated (ATM) variant carriers among breast cancer patients, raising numerous questions regarding use of breast radiation therapy (RT) in this population.Methods: A literature search using PubMed identified articles assessing association(s) between the germline ATM variant status and the risk of toxicity after breast RT. An expert panel of breast radiation oncologists, genetic counselors, and basic scientists convened to review the association between ATM variants and radiation-induced toxicity or secondary malignancy risk and to determine any impact on breast RT recommendations.Results: Carriers of pathogenic variants in ATMhave a 2- to 4-fold increased risk for developing breast cancer. ATMvariants do not consistently increase risks of toxicities after RT, except possibly among patients with the single nucleotide variant c5557G>A (rs1801516), in whoma small increased risk for the development of both acute and late radiation effects has been identified. In most breast cancer patientswith ATMvariants, the excess 5-year absolute risk of developing a secondary contralateral breast cancer (CBC) after radiation is extremely low. The exception is in women younger than 45 years old with deleterious rare ATM missense variants, who may be at higher risk for developing a radiation-induced CBC over time.Conclusions: Adjuvant radiation is safe for most breast cancer patients who harbor ATM variants. The possible exceptions are patients with the variant c5557G>A (rs1801516) and patients younger than 45 years old with certain rare deleterious ATM variants, who may be at higher risk for developing CBC. These latter patients should be counseled regarding this potential risk, and every effort should be made to minimize the contralateral breast dose. However, the inconsistency of published data limits precise recommendations, magnifying the need for further prospective studies and the development of a centralized database cataloging RT outcomes and genetic status. (C) 2021 Elsevier Inc. All rights reserved.