转移性乳腺癌患者中 及其他基因 panel 的突变——与患者及疾病特征的关联及其对预后的影响
Mutations in and Other Panel Genes in Patients With Metastatic Breast Cancer -Association With Patient and Disease Characteristics and Effect on Prognosis.
作者信息
Fasching Peter A, Yadav Siddhartha, Hu Chunling, Wunderle Marius, Häberle Lothar, Hart Steven N, Rübner Matthias, Polley Eric C, Lee Kun Y, Gnanaolivu Rohan D, Hadji Peyman, Hübner Hanna, Tesch Hans, Ettl Johannes, Overkamp Friedrich, Lux Michael P, Ekici Arif B, Volz Bernhard, Uhrig Sabrina, Lüftner Diana, Wallwiener Markus, Müller Volkmar, Belleville Erik, Untch Michael, Kolberg Hans-Christian, Beckmann Matthias W, Reis André, Hartmann Arndt, Janni Wolfgang, Wimberger Pauline, Taran Florin-Andrei, Fehm Tanja N, Wallwiener Diethelm, Brucker Sara Y, Schneeweiss Andreas, Hartkopf Andreas D, Couch Fergus J
机构信息
Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Department of Oncology, Mayo Clinic, Rochester, MN.
出版信息
J Clin Oncol. 2021 May 20;39(15):1619-1630. doi: 10.1200/JCO.20.01200. Epub 2021 Mar 29.
PURPOSE
Among patients with metastatic breast cancer (mBC), the frequency of germline mutations in cancer susceptibility genes and the clinical relevance of these mutations are unclear. In this study, a prospective cohort of patients with mBC was used to determine mutation rates for breast cancer (BC) predisposition genes, to evaluate the clinical characteristics of patients with mutations, and to assess the influence of mutations on patient outcome.
PATIENTS AND METHODS
Germline DNA from 2,595 patients with mBC enrolled in the prospective PRAEGNANT registry was evaluated for mutations in cancer predisposition genes. The frequencies of mutations in known BC predisposition genes were compared with results from a prospective registry of patients with nonmetastatic BC sequenced using the same QIAseq method and with public reference controls. Associations between mutation status and tumor characteristics, progression-free survival, and overall survival were assessed.
RESULTS
Germline mutations in 12 established BC predisposition genes (including and ) were detected in 271 (10.4%) patients. A mutation in or was seen in 129 patients (5.0%). mutation carriers had a higher proportion of brain metastasis (27.1%) compared with nonmutation carriers (12.8%). Mutations were significantly enriched in PRAEGNANT patients with mBC compared with patients with nonmetastatic BC (10.4% 6.6%, < .01). Mutations did not significantly modify progression-free survival or overall survival for patients with mBC.
CONCLUSION
Multigene panel testing may be considered in all patients with mBC because of the high frequency of germline mutations in and other BC predisposition genes. Although the prognosis of mutation carriers and nonmutation carriers with mBC was similar, differences observed in tumor characteristics have implications for treatment and for future studies of targeted therapies.
目的
在转移性乳腺癌（mBC）患者中，癌症易感基因种系突变的频率以及这些突变的临床相关性尚不清楚。在本研究中，使用mBC患者的前瞻性队列来确定乳腺癌（BC）易感基因的突变率，评估突变患者的临床特征，并评估突变对患者预后的影响。
患者与方法
对纳入前瞻性PRAEGNANT注册研究的2595例mBC患者的种系DNA进行癌症易感基因突变评估。将已知BC易感基因突变的频率与使用相同QIAseq方法测序的非转移性BC患者前瞻性注册研究结果以及公共参考对照进行比较。评估突变状态与肿瘤特征、无进展生存期和总生存期之间的关联。
结果
在271例（10.4%）患者中检测到12个已确定的BC易感基因（包括 和 ）的种系突变。129例患者（5.0%）检测到 或 突变。与非突变携带者（12.8%）相比， 突变携带者脑转移的比例更高（27.1%）。与非转移性BC患者相比，mBC的PRAEGNANT患者中突变显著富集（10.4%对6.6%，P<0.01）。突变对mBC患者的无进展生存期或总生存期没有显著影响。
结论
由于 和其他BC易感基因种系突变的频率较高，所有mBC患者都可考虑进行多基因检测。虽然mBC突变携带者和非突变携带者的预后相似，但在肿瘤特征方面观察到的差异对治疗和未来靶向治疗研究具有重要意义。
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