A prognostic model based on cell-cycle control predicts outcome of breast cancer patients.
Adult
Aged
Aged, 80 and over
Anaphase
/ genetics
Biomarkers, Tumor
/ analysis
Breast
/ pathology
Breast Neoplasms
/ genetics
Carcinoma, Ductal, Breast
/ genetics
Cell Cycle Checkpoints
/ genetics
Cell Cycle Proteins
/ analysis
Chemoradiotherapy, Adjuvant
Follow-Up Studies
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Mastectomy
Metaphase
/ genetics
Middle Aged
Models, Statistical
Breast cancer
Cell cycle
Prognosis
Proliferation
Securin
Separase
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
16 Jun 2020
16 Jun 2020
Historique:
received:
20
01
2020
accepted:
05
06
2020
entrez:
18
6
2020
pubmed:
18
6
2020
medline:
12
1
2021
Statut:
epublish
Résumé
A prognostic model combining biomarkers of metaphase-anaphase transition of the cell cycle was developed for invasive breast cancer. The prognostic value and clinical applicability of the model was evaluated in comparison with the routine prognosticators of invasive breast carcinoma. The study comprised 1135 breast cancer patients with complete clinical data and up to 22-year follow-up. Regulators of metaphase-anaphase transition were detected immunohistochemically and the biomarkers with the strongest prognostic impacts were combined into a prognostic model. The prognostic value of the model was tested and evaluated in separate patient materials originating from two Finnish breast cancer centers. The designed model comprising immunoexpressions of Securin, Separase and Cdk1 identified 8.4-fold increased risk of breast cancer mortality (p < 0.0001). A survival difference exceeding 15 years was observed between the majority (> 75%) of patients resulting with favorable as opposed to unfavorable outcome of the model. Along with nodal status, the model showed independent prognostic impact for all breast carcinomas and for subgroups of luminal, N+ and N- disease. The impact of the proposed prognostic model in predicting breast cancer survival was comparable to nodal status. However, the model provided additional information in N- breast carcinoma in identifying patients with aggressive course of disease, potentially in need of adjuvant treatments. Concerning N+, in turn, the model could provide evidence for withholding chemotherapy from patients with favorable outcome.
Sections du résumé
BACKGROUND
BACKGROUND
A prognostic model combining biomarkers of metaphase-anaphase transition of the cell cycle was developed for invasive breast cancer. The prognostic value and clinical applicability of the model was evaluated in comparison with the routine prognosticators of invasive breast carcinoma.
METHODS
METHODS
The study comprised 1135 breast cancer patients with complete clinical data and up to 22-year follow-up. Regulators of metaphase-anaphase transition were detected immunohistochemically and the biomarkers with the strongest prognostic impacts were combined into a prognostic model. The prognostic value of the model was tested and evaluated in separate patient materials originating from two Finnish breast cancer centers.
RESULTS
RESULTS
The designed model comprising immunoexpressions of Securin, Separase and Cdk1 identified 8.4-fold increased risk of breast cancer mortality (p < 0.0001). A survival difference exceeding 15 years was observed between the majority (> 75%) of patients resulting with favorable as opposed to unfavorable outcome of the model. Along with nodal status, the model showed independent prognostic impact for all breast carcinomas and for subgroups of luminal, N+ and N- disease.
CONCLUSIONS
CONCLUSIONS
The impact of the proposed prognostic model in predicting breast cancer survival was comparable to nodal status. However, the model provided additional information in N- breast carcinoma in identifying patients with aggressive course of disease, potentially in need of adjuvant treatments. Concerning N+, in turn, the model could provide evidence for withholding chemotherapy from patients with favorable outcome.
Identifiants
pubmed: 32546141
doi: 10.1186/s12885-020-07045-3
pii: 10.1186/s12885-020-07045-3
pmc: PMC7296704
doi:
Substances chimiques
Biomarkers, Tumor
0
Cell Cycle Proteins
0
Types de publication
Evaluation Study
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
558Références
Biology (Basel). 2017 Feb 08;6(1):
pubmed: 28208750
Tumour Biol. 2017 Mar;39(3):1010428317692233
pubmed: 28349831
Ann Oncol. 2013 Sep;24(9):2206-23
pubmed: 23917950
Br J Cancer. 2014 Jun 10;110(12):2905-13
pubmed: 24853182
Pathology. 2017 Feb;49(2):166-171
pubmed: 28065411
Front Oncol. 2019 Apr 24;9:310
pubmed: 31106147
Cancer Sci. 2007 May;98(5):644-51
pubmed: 17359284
Breast. 2015 Nov;24 Suppl 2:S26-35
pubmed: 26253814
Lancet Oncol. 2010 Feb;11(2):174-83
pubmed: 20152769
Appl Immunohistochem Mol Morphol. 2016 Oct;24(9):615-621
pubmed: 26447899
Dis Markers. 2013;35(4):267-72
pubmed: 24344401
Clin Cancer Res. 2009 Apr 15;15(8):2703-10
pubmed: 19351757
Expert Rev Mol Med. 2010 Dec 03;12:e38
pubmed: 21129230
PLoS One. 2011;6(8):e23754
pubmed: 21858218
Br J Cancer. 2014 Apr 2;110(7):1688-97
pubmed: 24619074
Br J Cancer. 2008 Jul 22;99(2):335-40
pubmed: 18594525
Ann Oncol. 2015 Aug;26(8):1533-46
pubmed: 25939896
J Pathol Clin Res. 2016 Jan 15;2(1):32-40
pubmed: 27499914
BMC Cancer. 2011 Jul 15;11:299
pubmed: 21762477
Oncotarget. 2016 Aug 2;7(31):49481-49497
pubmed: 27385216
Cancer Treat Rev. 2018 Jan;62:110-122
pubmed: 29202431
BMC Cancer. 2014 Dec 15;14:951
pubmed: 25511643
BMC Cancer. 2017 Oct 27;17(1):705
pubmed: 29078751
Arch Pathol Lab Med. 2014 Feb;138(2):241-56
pubmed: 24099077
Biol Rev Camb Philos Soc. 2017 Nov;92(4):2070-2083
pubmed: 28177203
Breast Cancer Res. 2008;10(4):R65
pubmed: 18662380
Medicine (Baltimore). 2017 May;96(19):e6860
pubmed: 28489780
Trends Cell Biol. 2017 Jan;27(1):42-54
pubmed: 27567180
Mol Cell. 2015 Nov 19;60(4):524-36
pubmed: 26590712
Br J Cancer. 2017 Oct 24;117(9):1383-1391
pubmed: 28859055
Oncogene. 2017 Sep 14;36(37):5296-5308
pubmed: 28504713
Anticancer Res. 2005 Jan-Feb;25(1A):121-5
pubmed: 15816528
Clin Cancer Res. 2014 Mar 1;20(5):1298-305
pubmed: 24520097
Curr Biol. 2015 Oct 19;25(20):R1002-18
pubmed: 26485365
Ann Oncol. 2009 Aug;20(8):1319-29
pubmed: 19535820
BMC Cancer. 2019 Mar 14;19(1):230
pubmed: 30871490
Int J Clin Exp Pathol. 2014 Jan 15;7(2):722-7
pubmed: 24551295