Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.
Hereditary Cancer Genetics Group, Vall d'Hebron Institute of Oncology (VHIO) and Medical Oncology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Hospital Campus, Barcelona, Spain.
Genet Med. 2021 Aug;23(8):1416-1423. doi: 10.1038/s41436-021-01151-8. Epub 2021 May 11.
PALB2 germline pathogenic variants are associated with increased breast cancer risk and smaller increased risk of pancreatic and likely ovarian cancer. Resources for health-care professionals managing PALB2 heterozygotes are currently limited.
A workgroup of experts sought to outline management of PALB2 heterozygotes based on current evidence. Peer-reviewed publications from PubMed were identified to guide recommendations, which arose by consensus and the collective expertise of the authors.
PALB2 heterozygotes should be offered BRCA1/2-equivalent breast surveillance. Risk-reducing mastectomy can be considered guided by personalized risk estimates. Pancreatic cancer surveillance should be considered, but ideally as part of a clinical trial. Typically, ovarian cancer surveillance is not recommended, and risk-reducing salpingo-oophorectomy should only rarely be considered before the age of 50. Given the mechanistic similarities, PALB2 heterozygotes should be considered for therapeutic regimens and trials as those for BRCA1/2.
This guidance is similar to those for BRCA1/2. While the range of the cancer risk estimates overlap with BRCA1/2, point estimates are lower in PALB2 so individualized estimates are important for management decisions. Systematic prospective data collection is needed to determine as yet unanswered questions such as the risk of contralateral breast cancer and survival after cancer diagnosis.
胚系 PALB2 致病性变异与乳腺癌风险增加相关，同时也使胰腺癌和可能的卵巢癌风险略有增加。目前，管理 PALB2 杂合子的医疗保健专业人员资源有限。
一个专家组旨在根据现有证据概述 PALB2 杂合子的管理方法。从 PubMed 中确定了经过同行评审的出版物，以指导建议的制定，这些建议是通过共识和作者的集体专业知识得出的。
应向 PALB2 杂合子提供与 BRCA1/2 等效的乳房监测。可以根据个人风险评估考虑进行预防性乳房切除术。应考虑进行胰腺癌监测，但理想情况下应作为临床试验的一部分。通常不建议进行卵巢癌监测，并且在 50 岁之前，只有极少数情况下才应考虑进行预防性输卵管卵巢切除术。鉴于机制相似性，应考虑将 PALB2 杂合子纳入 BRCA1/2 的治疗方案和临床试验中。
本指南与 BRCA1/2 相似。虽然癌症风险估计的范围与 BRCA1/2 重叠，但 PALB2 的点估计值较低，因此个体化估计对于管理决策很重要。需要系统地前瞻性收集数据，以确定尚未回答的问题，例如对侧乳腺癌的风险和癌症诊断后的生存情况。
