BRAF Mutations in Low-Grade Serous Ovarian Cancer and Response to BRAF Inhibition

被引：27

作者：

Moujaber, Tania ^{[1
,2
,3
]}

Etemadmoghadam, Dariush ^{[5
,6
]}

Kennedy, Catherine J. ^{[1
,2
,3
]}

Chiew, Yoke-Eng ^{[1
,2
,3
]}

Balleine, Rosemary L. ^{[1
,2
,3
,4
]}

Saunders, Catherine ^{[2
,3
]}

Wain, Gerard, V ^{[3
]}

Gao, Bo ^{[1
,3
]}

Hogg, Russell ^{[2
]}

Srirangan, Sivatharsny ^{[1
]}

Kan, Casina ^{[1
]}

Fereday, Sian ^{[5
]}

Traficante, Nadia ^{[5
]}

Patch, Ann-Marie ^{[9
]}

Pearson, John, V ^{[9
]}

Waddell, Nicola ^{[9
]}

Grimmond, Sean M. ^{[6
]}

Dobrovic, Alexander ^{[6
,7
,8
]}

Bowtell, David D. L. ^{[5
,6
,10
]}

Harnett, Paul R. ^{[1
,2
,3
]}

DeFazio, Anna ^{[1
,2
,3
]}

Bowtell, D. ^{[10
,11
,12
]}

Chenevix-Trench, G. ^{[13
]}

Green, A. ^{[13
]}

Webb, P. ^{[13
]}

DeFazio, A. ^{[14
,15
]}

Gertig, D. ^{[12
]}

Traficante, N. ^{[11
,16
]}

Fereday, S. ^{[11
,16
]}

Moore, S. ^{[13
]}

Harrap, K. ^{[13
]}

Sadkowsky, T. ^{[13
]}

Pandeya, N. ^{[13
]}

Hung, J. ^{[15
]}

Malt, M. ^{[13
]}

Alexander, B. ^{[13
]}

Ashover, E. ^{[13
]}

Brown, S. ^{[13
]}

Corrish, T. ^{[13
]}

Green, L. ^{[13
]}

Jackman, L. ^{[13
]}

Ferguson, K. ^{[13
]}

Martin, K. ^{[13
]}

Martyn, A. ^{[13
]}

Ranieri, B. ^{[13
]}

Mellon, A. ^{[17
]}

Robertson, R. ^{[17
]}

Vanden Bergh, T. ^{[18
]}

Jones, M. ^{[18
]}

Mackenzie, P. ^{[18
]}

机构：

[1] Westmead Inst Med Res, Westmead, NSW, Australia

[2] Univ Sydney, Westmead, NSW, Australia

[3] Westmead Hosp, Westmead, NSW, Australia

[4] New South Wales Hlth Pathol, Westmead, NSW, Australia

[5] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia

[6] Univ Melbourne, Melbourne, Vic, Australia

[7] Olivia Newton John Canc Res Inst, Melbourne, Vic, Australia

[8] La Trobe Univ, Bundoora, Vic, Australia

[9] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia

[10] Imperial Coll London, London, England

[11] Peter MacCallum Canc Ctr, East Melbourne, Vic, Australia

[12] Univ Melbourne, Parkville, Vic, Australia

[13] QIMR Berghoier Med Res Inst, Brisbane, Qld, Australia

[14] Univ Sydney, Westmead Inst Med Res, Sydney, NSW, Australia

[15] Westmead Hosp, Sydney, NSW, Australia

[16] Peter MacCallurn Canc Ctr, East Melbourne, Vic, Australia

[17] John Hunter Hosp, New Lambton, NSW, Australia

[18] Royal Hosp Women, Randwick, NSW, Australia

[19] Royal North Shore Hosp, St Leonards, NSW, Australia

[20] Royal Prince Alfred Hosp, Camperdown, NSW, Australia

[21] Royal Adelaide Hosp, Adelaide, SA, Australia

[22] Royal Hobart Hosp, Hobart, Tas, Australia

[23] Monash Med Ctr, Clayton, Vic, Australia

[24] King Edward Mem Hosp, Subiaco, WA, Australia

[25] St John God Pathol, Osborne Pk, WA, Australia

[26] St John God Hosp, Subiaco, WA, Australia

[27] Canberra Hosp, Garran, ACT, Australia

[28] Bankstown Hosp, Bankstown, NSW, Australia

[29] Integrated Canc Ctr, Wahroonga, NSW, Australia

[30] Wollongong Hosp, Wollongong, NSW, Australia

[31] Nepean Hosp, Kingswood, NSW, Australia

[32] Newcastle Mater Misericordiae Hosp, Waratah, NSW, Australia

[33] Port Macquarie Base Hosp, Port Macquarie, NSW, Australia

[34] St George Hosp, Kogarah, NSW, Australia

[35] St Vincents Hosp, Darlinghurst, NSW, Australia

[36] Wagga Wagga Base Hosp, Wagga Wagga, NSW, Australia

[37] Prince Wales Hosp, Sydney, NSW, Australia

[38] Mater Misericordiae Univ Hosp, South Brisbane, Qld, Australia

[39] Royal Brisbane & Womens Hosp, Herston, Qld, Australia

[40] Wesley Hosp, Auchenflower, Qld, Australia

[41] Burnside Hosp, Toorak Gardens, SA, Australia

[42] Flinders Med Ctr, Bedford Pk, SA, Australia

[43] Queen Elizabeth Hosp, Woodville South, SA, Australia

[44] Freemasons Hosp, East Melbourne, Vic, Australia

[45] Mercy Hosp Women, Heidelberg, Vic, Australia

[46] Royal Womens Hosp, Parkville, Vic, Australia

[47] Border Med Oncol, Wodonga, Vic, Australia

[48] Andrew Love Canc Ctr, Geelong, Vic, Australia

[49] Ballarat Base Hosp, Ballarat, Vic, Australia

[50] Bendigo Hlth Care Grp, Bendigo, Vic, Australia

来源：

JCO PRECISION ONCOLOGY | 2018年 / 2卷

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

SOLID TUMORS; COLON-CANCER; OPEN-LABEL; VEMURAFENIB; DABRAFENIB; CARCINOMA; MELANOMA; SURVIVAL; NRAS; RESPONSIVENESS;

D O I：

10.1200/PO.17.00221

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose Low-grade serous ovarian carcinoma (LGSC) responds poorly to chemotherapy and is characterized by activating mutations in the Ras sarcoma-mitogen-activated protein kinase (RAS-MAPK) pathway, including oncogenic BRAF. However, response to BRAF inhibitors is tumor-type specific. Significant improvement in survival is seen in patients with BRAF-mutant melanoma, but other cancer types, such as colorectal cancers, are generally less sensitive. We examined the frequency and characteristics of BRAF-mutated LGSC and described the response to treatment with BRAF inhibitors. Patients and Methods Mutations were assessed in LGSC (N = 65) by using targeted, exome, and whole-genome sequencing. Patient characteristics, treatment, and clinical outcome were assessed, and the median follow-up time was more than 5 years. BRAF inhibitors were trialed in two patients with a somatic BRAF V600E mutation: one patient received dabrafenib monotherapy and was monitored clinically, biochemically (cancer antigen [CA]-125 levels), and with positron emission tomography (PET) imaging. Expression of the BRAF V600E protein in this patient was assessed by immunohistochemistry. Results Among patients with LGSC, nine (13.8%) of 65 had a somatic BRAF mutation. Of the nine patients with BRAF mutation-positive LGSC, four experienced progressive disease that did not respond to conventional chemotherapy. Two of the patients experienced progression quickly and died as a result of disease progression, and two received targeted treatment. Two patients with BRAF V600E mutation received BRAF inhibitors at relapse and both achieved durable responses. Conclusion BRAF mutations are not uncommon in patients with LGSC and should be routinely tested, because BRAF inhibitors can be an effective treatment for these patients. The results highlight the need for targeted treatment in this rare tumor type, and a prospective study is needed to formally assess the response rate and clinical benefit. (C) 2018 by American Society of Clinical Oncology

引用

页码：1 / 14

页数：14

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