The TRAR gene classifier to predict response to neoadjuvant therapy in HER2-positive and ER-positive breast cancer patients: an explorative analysis from the NeoSphere trial.
HER2
breast cancer
gene expression profile
pertuzumab
predictive biomarker
trastuzumab
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
revised:
13
10
2021
received:
25
06
2021
accepted:
22
11
2021
pubmed:
25
11
2021
medline:
22
6
2022
entrez:
24
11
2021
Statut:
ppublish
Résumé
As most erb-b2 receptor tyrosine kinase 2 (HER2)-positive breast cancer (BC) patients currently receive dual HER2-targeting added to neoadjuvant chemotherapy, improved methods for identifying individual response, and assisting postsurgical salvage therapy, are needed. Herein, we evaluated the 41-gene classifier trastuzumab advantage risk model (TRAR) as a predictive marker for patients enrolled in the NeoSphere trial. TRAR scores were computed from RNA of 350 pre- and 166 post-treatment tumor specimens. Overall, TRAR score was significantly associated with pathological complete response (pCR) rate independently of other predictive clinico-pathological variables. Separate analyses according to estrogen receptor (ER) status showed a significant association between TRAR score and pCR in ER-positive specimens but not in ER-negative counterparts. Among ER-positive BC patients not achieving a pCR, those with TRAR-low scores in surgical specimens showed a trend for lower distant event-free survival. In conclusion, in HER2-positive/ER-positive BC, TRAR is an independent predictor of pCR and represents a promising tool to select patients responsive to anti-HER2-based neoadjuvant therapy and to assist treatment escalation and de-escalation strategies in this setting.
Identifiants
pubmed: 34816585
doi: 10.1002/1878-0261.13141
pmc: PMC9208076
doi:
Substances chimiques
Receptor, ErbB-2
EC 2.7.10.1
Trastuzumab
P188ANX8CK
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2355-2366Informations de copyright
© 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
Références
Ann Oncol. 2013 Nov;24(11):2715-24
pubmed: 23908178
Nat Rev Clin Oncol. 2017 Nov;14(11):669-681
pubmed: 28762384
Dis Markers. 2017;2017:7849108
pubmed: 29403144
Clin Cancer Res. 2016 Jan 15;22(2):337-45
pubmed: 26423797
Lancet Oncol. 2014 Jun;15(7):747-56
pubmed: 24794243
Lancet Oncol. 2016 Jun;17(6):791-800
pubmed: 27179402
Lancet Oncol. 2012 Jan;13(1):25-32
pubmed: 22153890
N Engl J Med. 2019 Feb 14;380(7):617-628
pubmed: 30516102
Front Oncol. 2019 Sep 25;9:967
pubmed: 31598491
Breast Cancer Res. 2017 Feb 9;19(1):16
pubmed: 28183321
J Clin Oncol. 2020 Dec 10;38(35):4184-4193
pubmed: 33095682
Breast Cancer Res. 2014 Jul 08;16(4):R73
pubmed: 25005255
Clin Cancer Res. 2014 Nov 1;20(21):5359-64
pubmed: 25204553
Ann Oncol. 2015 Dec;26(12):2429-36
pubmed: 26387142
Oncotarget. 2015 Sep 29;6(29):28173-82
pubmed: 26334217
Breast Cancer Res. 2013 Feb 07;15(1):R11
pubmed: 23391338
Future Oncol. 2016 Jun;12(11):1413-28
pubmed: 27007660
Lancet. 2012 Feb 18;379(9816):633-40
pubmed: 22257673
Breast Care (Basel). 2013 Aug;8(4):256-62
pubmed: 24415978
Clin Cancer Res. 2020 Jun 15;26(12):2783-2788
pubmed: 32046997
J Natl Cancer Inst. 2003 Jan 15;95(2):142-53
pubmed: 12529347
J Clin Oncol. 2008 Sep 1;26(25):4063-71
pubmed: 18678838
Nat Med. 2015 Oct;21(10):1128-38
pubmed: 26444637
JAMA Oncol. 2017 Feb 01;3(2):227-234
pubmed: 27684533
J Clin Oncol. 2009 Jul 1;27(19):3185-91
pubmed: 19364972
Clin Cancer Res. 2004 Sep 1;10(17):5650-5
pubmed: 15355889
J Clin Oncol. 2009 Dec 1;27(34):5838-47
pubmed: 19884552
Lancet Oncol. 2014 Feb;15(2):e58-68
pubmed: 24480556
Eur J Cancer. 2019 Sep;118:1-9
pubmed: 31284184
Nat Commun. 2020 Jan 20;11(1):385
pubmed: 31959756