Molecular Guided Treatments in Gynecologic Oncology: Analysis of a Real-World Precision Cancer Medicine Platform.
Gynecologic oncology
Immunohistochemistry
Molecular aberrations
Molecular profiling
Precision medicine
Targeted agents
Journal
The oncologist
ISSN: 1549-490X
Titre abrégé: Oncologist
Pays: England
ID NLM: 9607837
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
24
11
2019
accepted:
30
03
2020
pubmed:
6
5
2020
medline:
22
6
2021
entrez:
6
5
2020
Statut:
ppublish
Résumé
Advanced gynecologic cancers have a poor prognosis and constitute a major challenge for adequate treatment strategies. By analyzing and targeting molecular alterations, molecular guided treatments may be a viable option for the treatment of advanced gynecologic cancers. In this single-center, real-world retrospective analysis of our platform for precision cancer medicine (PCM), we describe the molecular profiling of 72 patients diagnosed with different types of advanced gynecologic malignancies. Tumor samples of the patients were examined by next-generation sequencing panel and immunohistochemistry (IHC). In total, we identified 209 genetic aberrations in 72 patients. The ten most frequent alterations were TP53 (n = 42, 20%), KRAS (n = 14, 6.6%), PIK3CA (n = 11, 5.2%), PIK3R1 (n = 9, 4.3%), ATR (n = 8, 3.8%), PTEN (n = 8, 3.8%), BRCA1 (n = 6, 2.8%), NF1 (n = 4, 1.9%), NOTCH1 (n = 4, 1.9%), and POLE (n = 4, 1.9%), which account for more than half of all molecular alterations (52.6%). In 21 (29.1%) patients only one mutation could be detected, and 44 (61.1%) patients had more than one mutation. No molecular alterations were detected in seven (9.7%) patients. IHC detected expression of phosphorylated mammalian target of rapamycin and epidermal growth factor receptor in 58 (80.6%) and 53 (73.6%) patients, respectively. In over two thirds (n = 49, 68.1%), a targeted therapy was suggested, based on the identified genetic aberrations. The most frequently recommended specific treatment was the combination of everolimus with exemestane (n = 18, 25 %). Based on our observations, it seems that PCM might be a feasible approach for advanced gynecologic cancers with limited treatment options. Nowadays molecular profiling of advanced gynecologic malignancies is feasible in the clinical routine. A molecular portrait should be done for every patient with an advanced therapy-refractory gynecologic malignancy to offer molecular-based treatment concepts.
Identifiants
pubmed: 32369643
doi: 10.1634/theoncologist.2019-0904
pmc: PMC7356753
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1060-e1069Informations de copyright
© 2020 The Authors. The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.
Références
Anticancer Res. 2010 Sep;30(9):3243-7
pubmed: 20944093
Oncotarget. 2016 Apr 19;7(16):21556-69
pubmed: 26933808
Gynecol Oncol. 2019 Jun;153(3):555-561
pubmed: 30929823
JAMA Oncol. 2018 Oct 1;4(10):1367-1374
pubmed: 29862411
Clin Cancer Res. 2018 Dec 1;24(23):5939-5947
pubmed: 30068706
Clin Cancer Res. 2014 Sep 1;20(17):4488-98
pubmed: 24687921
Clin Transl Oncol. 2018 Jun;20(6):753-760
pubmed: 29116433
Gynecol Oncol. 2016 Apr;141(1):2-9
pubmed: 27016222
Gynecol Oncol. 2019 Feb;152(2):243-250
pubmed: 30522700
J Clin Oncol. 2017 Dec 20;35(36):4035-4041
pubmed: 29095678
Theranostics. 2019 May 31;9(14):4130-4140
pubmed: 31281536
Breast. 2017 Oct;35:115-121
pubmed: 28711793
Lancet Oncol. 2016 Jan;17(1):78-89
pubmed: 26590673
Future Oncol. 2012 Jun;8(6):651-7
pubmed: 22764762
F1000Res. 2019 Jun 12;8:
pubmed: 31231511
Ann Oncol. 2019 May 1;30(5):766-773
pubmed: 30796821
J Clin Oncol. 2010 Nov 20;28(33):4877-83
pubmed: 20921468
Semin Cancer Biol. 2019 Apr;55:16-27
pubmed: 29857039
J Cell Mol Med. 2016 Apr;20(4):581-93
pubmed: 26800494
N Engl J Med. 2015 Aug 20;373(8):726-36
pubmed: 26287849
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Eur J Cancer. 2016 Jan;53:51-64
pubmed: 26693899
Cancer Manag Res. 2019 Apr 16;11:3061-3078
pubmed: 31114351
Clin Breast Cancer. 2010 Dec 1;10(6):489-91
pubmed: 21147694
Maturitas. 2013 Dec;76(4):308-14
pubmed: 24128673
Lancet Oncol. 2018 Aug;19(8):1126-1134
pubmed: 30026002
Chronic Dis Transl Med. 2015 Mar 21;1(1):14-17
pubmed: 29062982
J Clin Oncol. 2019 Jun 10;37(17):1470-1478
pubmed: 30943124
Sci Rep. 2019 Jul 18;9(1):10426
pubmed: 31320709
N Engl J Med. 2018 Dec 27;379(26):2495-2505
pubmed: 30345884
Front Pharmacol. 2019 Feb 01;10:65
pubmed: 30774597
Int J Cancer. 2019 Feb 15;144(4):877-885
pubmed: 29992557
Nat Med. 2018 Oct;24(10):1611-1624
pubmed: 30150718
Gynecol Oncol. 2010 Feb;116(2):163-7
pubmed: 19740535
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
N Engl J Med. 2019 Dec 19;381(25):2391-2402
pubmed: 31562799
Gynecol Oncol. 2014 Aug;134(2):274-80
pubmed: 24882554
Gynecol Oncol. 2016 Apr;141(1):24-8
pubmed: 27016225