Clinicopathologic features and outcomes of patients with lung adenocarcinomas harboring BRAF mutations in the Lung Cancer Mutation Consortium. Issue 3 (1st October 2014)

• Record Type: Journal Article
• Authors: Villaruz, Liza C.; Socinski, Mark A.; Abberbock, Shira; Berry, Lynne D.; Johnson, Bruce E.; Kwiatkowski, David J.; Iafrate, A. John; Varella‐Garcia, Marileila; Franklin, Wilbur A.; Camidge, D. Ross; Sequist, Lecia V.; Haura, Eric B.; Ladanyi, Mark; Kurland, Brenda F.; Kugler, Kelly; Minna, John D.; Bunn, Paul A.; Kris, Mark G.
• Is Part Of: Cancer. Volume 121:Issue 3(2015)
• Page Start: 448
• Page End: 456
• Publication Date: 2014-10-01
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.29042
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cncr29042-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>The advent of effective targeted therapy for <italic>BRAF<sup>V600E</sup></italic>‐mutant lung adenocarcinomas necessitates further exploration of the unique clinical features and behavior of advanced‐stage <italic>BRAF</italic>‐mutant lung adenocarcinomas.</p> </sec> <sec id="cncr29042-sec-0002" sec-type="section"> <title>METHODS</title> <p>Data were reviewed for patients with advanced lung adenocarcinomas enrolled in the Lung Cancer Mutation Consortium whose tumors underwent testing for mutations in epidermal growth factor receptor (<italic>EGFR</italic>), Kirsten rat sarcoma viral oncogene homolog (<italic>KRAS</italic>), human epidermal growth factor receptor 2 (<italic>HER2</italic>), <italic>AKT1</italic>, <italic>BRAF</italic>, dual‐specificity mitogen‐activated protein kinase kinase 1 (<italic>MEK1</italic>), neuroblastoma RAS viral (v‐ras) oncogene homolog (<italic>NRAS</italic>), and phosphatidylinositol‐4, 5‐bisphosphate 3‐kinase catalytic subunit α (<italic>PIK3CA</italic>); for anaplastic lymphoma kinase (<italic>ALK</italic>) translocations; and for <italic>MET</italic> amplification.</p> </sec> <sec id="cncr29042-sec-0003" sec-type="section"> <title>RESULTS</title> <p>Twenty‐one <italic>BRAF</italic> mutations were identified in 951 patients with adenocarcinomas (2.2%; 95% confidence interval [CI], 1.4%‐3.4%): 17 (81%; 95% CI, 60%‐92%) were <italic>BRAF<sup>V600E</sup></italic> mutations, and 4 were non‐<italic>BRAF<sup>V600E</sup></italic> mutations. Among the 733 cases tested for all 10 genes, <italic>BRAF</italic> mutations were more likely to occur than most other genotypic abnormalities in current or former smokers (<italic>BRAF</italic> vs sensitizing <italic>EGFR</italic>, 82% vs 36%, mid‐<italic>P</italic> < .001; <italic>BRAF</italic> vs <italic>ALK</italic>, 39%, mid‐<italic>P</italic> = .003; <italic>BRAF</italic> vs other mutations, 49%, mid‐<italic>P</italic> = .02; <italic>BRAF</italic> vs patients with more than 1 oncogenic driver [doubleton], 46%, mid‐<italic>P</italic> = .04.) The double‐mutation rate was 16% among patients with <italic>BRAF</italic> mutations but 5% among patients with other genomic abnormalities (mid‐<italic>P</italic> = .045). Differences were not found in survival between patients with <italic>BRAF</italic> mutations and those with other genomic abnormalities (<italic>P</italic> > .20).</p> </sec> <sec id="cncr29042-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p> <italic>BRAF</italic> mutations occurred in 2.2% of advanced‐stage lung adenocarcinomas, were most commonly <italic>V600E</italic>, and were associated with distinct clinicopathologic features in comparison with other genomic subtypes and with a high mutation rate in more than 1 gene. These findings underscore the importance of comprehensive genomic profiling in assessing patients with advanced lung adenocarcinomas. <bold><italic>Cancer</italic> 2015;121:448–456.</bold> © <italic>2014 American Cancer Society</italic>.</p> </sec> </abstract>