美国医学会杂志肿瘤学分册基因检测在乳腺癌 [复制链接]

　　由于乳腺癌天然异质性与临床适用性存在问题，故乳腺肿瘤体细胞突变新一代测序（NGS）基因检测的应用一直慢于预期。

　　年8月25日，《美国医学会杂志肿瘤学分册》在线发表贝勒医学院莱斯特与苏·史密斯乳腺中心的综述，总结了该领域的现状，并探讨了更有效的实现方法。

　　虽然生殖细胞基因检测可能预测铂类和PARP抑制剂的敏感性，但是预测药物敏感性的体细胞突变数据仍然存在争议。目前，尚无任何指南或监管部门批准用于指导治疗的体细胞基因组肿瘤突变检测。然而，某些小样本人群出现希望，例如那些具有ERBB2/HER2突变、可能成为阳性药物体细胞突变匹配的首选人群。同样，那些ESR1突变可能与芳香酶抑制剂治疗效果存在反比关系。转移性疾病是需要特别
　　循环肿瘤DNA分析一旦足够敏感和广泛，将加快乳腺癌治疗相关NGS技术需求的进展。将体细胞突变与临床和药物数据进行全面结合的广泛协作联盟，将是进展的关键。作者建议建立一个百科全书式的开源数据库，作为NGS测序报告解读的参考，并提供给所有临床医生以帮助指导治疗。

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乳腺癌十大最常见突变基因

排名及其潜在相关治疗意义

JAMAOncol.Aug25.[Epubaheadofprint]

TheRoleofGeneticTestingintheSelectionofTherapyforBreastCancer:AReview.

NiravathP,CakarB,EllisM.

LesterandSueSmithBreastCenter,BaylorCollegeofMedicine,Houston,Texas.

Importanceheapplicationofnext-generationsequencing(NGS)genomictestingforsomaticmutationsinbreastoncologyhasbeenslowerthananticipatedduetoissueswithclinicalapplicabilityandnaturalheterogeneityofbreastcancer.Thisreviewsummarizesthestateofthefieldandconsidersapproachesformoreeffectiveimplementation.

Observations:WhilethereisanemergingroleforgermlinegenetictestingpotentiallypredictingsensitivitytoplatinumsaltsandPARPinhibitors,thedataregardingsomaticmutationforpredictionofdrugsensitivityremainscontroversial.Currently,therearenoguidelinesorregulatoryapprovalsforgenomicsomatictumormutationtestingtodirecttherapy.However,somesmallpopulationsshowpromise,suchasthosewithERBB2/HER2mutationwhomayrepresentthefirstpopulationtohaveapositivedrugsomaticmutationmatch.Similarly,thosewithESR1mutationmaybethefirsttoemergeforanegativeassociationwiththeefficacyofaromatase-inhibitortreatment.Oneofthebarrierstoprogressisthenecessaryfocusonmetastaticdisease,whichisoftenchallenging,expensive,andriskytobiopsy.Inaddition,becauseoftheclonalheterogeneityofadvanceddisease,asinglesamplemaynotcontainallthegenomicinformationnecessaryfortreatment.Thus,circulatingtumorDNAanalysisisperhapsoneofthemostpracticalandpromisingapproaches.

ConclusionsandRelevance:CirculatingtumorDNAanalysis,oncesensitiveandbroadenough,willaccelerateprogressinthequesttomakeNGStechnologiesrelevanttobreastcancertreatment.Abroadandcoordinatedcoalitiontosystematicallyconnectsomaticmutationstoclinicalandpharmacologicdatawillbecriticalforprogress.Were