Please use this identifier to cite or link to this item:
https://repository.monashhealth.org/monashhealthjspui/handle/1/36861| Title: | BRAF mutations in low-grade serous ovarian cancer and response to BRAF inhibition. | Authors: | Jones M.;Patch A.-M.;Alsop K.;Ball C.;Young C.;Schmidt T.;Shirley H.;Viduka S.;Bilic S.;Glavinas L.;Brooks J.;Traficante N.;Stuart-Harris R.;Kirsten F.;Rutovitz J.;Clingan P.;Glasgow A.;Valmadre S.;Young B.;Camaris C.;Crouch R.;Edwards L.;Hacker N.;Marsden D.;Robertson G.;Beale P.;Beith J.;Carter J.;Dalrymple C.;Houghton R.;Russell P.;Links M.;Grygiel J.;Hill J.;Brand A.;Byth K.;Jaworski R.;Sharma R.;Harnett P.;Wain G.;Friedlander M.;Ward B.;Papadimos D.;Crandon A.;Cummings M.;Horwood K.;Obermair A.;Perrin L.;Wyld D.;Nicklin J.;Davy M.;Oehler M.K.;Hall C.;Dodd T.;Healy T.;Pittman K.;Henderson D.;Miller J.;Pierdes J.;Blomfield P.;Challis D.;McIntosh R.;Parker A.;Brown B.;Rome R.;Allen D.;Grant P.;Hyde S.;Laurie R.;Robbie M.;Healy D.;Manolitsas T.;McNealage J.;Rogers P.;Susil B.;Sumithran E.;Simpson I.;Phillips K.;Rischin D.;Fox S.;Johnson D.;Lade S.;Loughrey M.;O'Callaghan N.;Murray W.;Waring P.;Billson V.;Pyman J.;Neesham D.;Quinn M.;Underhill C.;Ng L.F.;Blum R.;Ganju V.;Hammond I.;Leung Y.;McCartney A. ;Buck M.;Haviv I.;Purdie D.;Whiteman D.;Zeps N.;Bell R. ;Jobling T. ;Tran H. ;Moujaber T.;Etemadmoghadam D.;Kennedy C.J.;Chiew Y.E.;Balleine R.L.;Saunders C.;Wain G.V.;Gao B.;Hogg R.;Srirangan S.;Kan C.;Fereday S.;Pearson J.V.;Waddell N.;Grimmond S.M.;Dobrovic A.;Bowtell D.D.L.;Harnett P.R.;deFazio A.;Bowtell D.;Chenevix-Trench G.;Green A.;Webb P.;Gertig D.;Moore S.;Harrap K.;Sadkowsky T.;Pandeya N.;Hung J.;Malt M.;Alexander B.;Ashover P.;Brown S.;Corrish T.;Green L.;Jackman L.;Ferguson K.;Martin K.;Martyn A.;Ranieri B.;Mellon A.;Robertson R.;Vanden Bergh T.;Mackenzie P.;Maidens J.;Nattress K.;Stenlake A.;Sullivan H.;White J.;Jayde V.;Mamers P.;Bowes L.;Galletta L.;Giles D.;Hendley J.;Proietto A.;Braye S.;Otton G.;Shannon J.;Bonaventura T.;Stewart J.;Begbie S.;Bell D.;Baron-Hay S.;Ferrier A.;Gard G.;Nevell D.;Pavlakis N. | Institution: | (Moujaber, Kennedy, Chiew, Balleine, Gao, Srirangan, Kan, Harnett, deFazio) Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Sydney, NSW, Australia (Moujaber, Kennedy, Chiew, Balleine, Saunders, Hogg, deFazio) University of Sydney, Australia (Moujaber, Kennedy, Chiew, Chiew, Balleine, Saunders, Wain, Gao, Harnett, deFazio, Hung, Stenlake, Sullivan, Brand, Byth, Jaworski, Sharma, Harnett, Wain) Westmead Hospital, Westmead, Sydney, NSW, Australia (Balleine) New South Wales Health Pathology, Westmead, NSW, United States (Etemadmoghadam, Fereday, Fereday, Traficante, Traficante, Bowtell, Bowtell, Bowes, Galletta, Giles, Hendley, Alsop, Phillips, Rischin, Fox, Johnson, Lade, Loughrey, O'Callaghan, Murray) Peter MacCallum Cancer Centre, East Melbourne and University of Melbourne, Parkville, VIC, Australia (Etemadmoghadam, Grimmond, Dobrovic, Bowtell, Gertig, Waring) University of Melbourne, Parkville, VIC, Australia (Dobrovic) Olivia Newton John Cancer Research Institute, Heidelberg, Melbourne, Australia (Dobrovic) La Trobe University, Bundoora, VIC, Australia (Patch, Pearson, Waddell, Chenevix-Trench, Green, Webb, Moore, Harrap, Sadkowsky, Pandeya, Malt, Alexander, Ashover, Brown, Corrish, Green, Jackman, Ferguson, Martin, Martyn, Ranieri, Purdie, Whiteman) QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia (Bowtell, Bowtell) Imperial College London, London, England, United Kingdom (Mellon, Robertson, Proietto, Braye, Otton) John Hunter Hospital, New Lambton, NSW, Australia (Vanden Bergh, Jones, Mackenzie, Camaris, Crouch, Edwards, Hacker, Marsden, Robertson) Royal Hospital for Women, Randwick, NSW, Australia (Maidens, Bell, Baron-Hay, Ferrier, Gard, Nevell, Pavlakis, Valmadre, Young) Royal North Shore Hospital, St Leonards, NSW, Australia (Nattress, Beale, Beith, Carter, Dalrymple, Houghton, Russell) Royal Prince Alfred Hospital, Camperdown, NSW, Australia (White, Davy, Oehler, Hall, Dodd) Royal Adelaide Hospital, Adelaide, SA, Australia (Jayde, Blomfield, Challis, McIntosh, Parker) Royal Hobart Hospital, Hobart, TAS, Australia (Mamers, Healy, Jobling, Manolitsas, McNealage, Rogers, Susil, Sumithran, Simpson) Monash Medical Centre, Clayton, VIC, Australia (Ball, Young, Hammond, Leung, McCartney) King Edward Memorial Hospital, Subiaco, WA, Australia (Schmidt, Shirley, Viduka, Tran, Bilic, Glavinas, Zeps) St John of God Pathology, Osborne Park, WA, Australia (Brooks) St John of God Hospital, Subiaco, WA, Australia (Stuart-Harris) Canberra Hospital, Garran, ACT, Australia (Kirsten) Bankstown Hospital, Bankstown, NSW, Australia (Rutovitz) Integrated Cancer Centre, Wahroonga, NSW, Australia (Clingan, Glasgow) Wollongong Hospital, Wollongong, NSW, Australia (Shannon) Nepean Hospital, Kingswood, NSW, Australia (Bonaventura, Stewart) Newcastle Mater Misericordiae Hospital, Waratah, NSW, Australia (Begbie) Port Macquarie Base Hospital, Port Macquarie, NSW, Australia (Links) St George Hospital, Kogarah, NSW, Australia (Grygiel) St Vincent's Hospital, Darlinghurst, NSW, Australia (Hill) Wagga Wagga Base Hospital, Wagga Wagga, NSW, Australia (Friedlander) Prince of Wales Hospital, Sydney, Australia (Ward, Papadimos) Mater Misericordiae Hospital, South Brisbane, QLD, Australia (Crandon, Cummings, Horwood, Obermair, Perrin, Wyld, Nicklin) The Royal Brisbane and Women's Hospital, Herston, QLD, Australia (Nicklin) Wesley Hospital, Auchenflower, QLD, Australia (Healy, Pittman) Burnside Hospital, Toorak Gardens, SA, Australia (Henderson) Flinders Medical Centre, Bedford Park, SA, Australia (Miller, Pierdes) Queen Elizabeth Hospital, Woodville South, SA, Australia (Brown, Rome) Freemasons Hospital, East Melbourne, VIC, Australia (Allen, Grant, Hyde, Laurie, Robbie) Mercy Hospital for Women, Heidelberg, VIC, Australia (Billson, Pyman, Neesham, Quinn) The Royal Women's Hospital, Parkville, VIC, Australia (Underhill) Border Medical Oncology, Wodonga, VIC, Australia (Bell) Andrew Love Cancer Centre, Geelong, VIC, Australia (Ng) Ballarat Base Hospital, Ballarat, VIC, Australia (Blum) Bendigo Health Care Group, Bendigo, VIC, Australia (Ganju) Peninsula Health, Frankston, VIC, Australia (Buck) Mount Hospital, Perth, WA, Australia (Haviv) Bar-Ilan University, Safed, Israel | Issue Date: | 13-Sep-2019 | Copyright year: | 2018 | Publisher: | American Society of Clinical Oncology | Place of publication: | United States | Publication information: | JCO Precision Oncology. 2 (no pagination), 2018. Date of Publication: 01 Jan 2018. | Abstract: | 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.Copyright © 2019 American Society of Clinical Oncology. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1200/PO.17.00221 | ISSN: | 2473-4284 (electronic) | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/36861 | Type: | Article |
| Appears in Collections: | Articles |
Show full item record
Items in Monash Health Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.