Influence of XRCC4 expression by breast cancer cells on ipsilateral recurrence after breast-conserving therapy.
Einfluss der XRCC4-Expression von Brustkrebszellen auf ipsilaterale Rezidive nach brusterhaltender Therapie.
Adult
Aged
Breast Neoplasms
/ genetics
Carcinoma, Ductal
/ genetics
Carcinoma, Lobular
/ genetics
Cohort Studies
DNA-Binding Proteins
/ genetics
Female
Humans
Mastectomy, Segmental
Middle Aged
Neoplasm Recurrence, Local
/ genetics
Neoplasm Staging
Neoplasms, Second Primary
/ genetics
Prognosis
Propensity Score
Survival Rate
DNA repair
New primary tumor
Nonhomologous end-joining (NHEJ) proteins
Radiotherapy
True recurrence
Journal
Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]
ISSN: 1439-099X
Titre abrégé: Strahlenther Onkol
Pays: Germany
ID NLM: 8603469
Informations de publication
Date de publication:
Jul 2019
Jul 2019
Historique:
received:
25
01
2019
accepted:
29
03
2019
pubmed:
19
4
2019
medline:
15
1
2020
entrez:
19
4
2019
Statut:
ppublish
Résumé
We examined the expression of nonhomologous end-joining (NHEJ) proteins by breast cancer cells in patients with or without ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy. We also investigated whether there was a difference of NHEJ-related protein expression by tumor cells between two types of IBTR, i.e., true recurrence (TR) with regrowth from the tumor bed or development of a new primary tumor (NP). The original cohort comprised 560 breast cancer patients who received breast-conserving therapy between February 1995 and March 2006, including 520 patients without IBTR and 40 patients with IBTR. Propensity score matching was employed to select 40 trios (120 patients) consisting of 1 patient with IBTR and 2 patients without IBTR. Immunohistochemical examination of proteins related to NHEJ was performed in surgical specimens. The 40 patients with IBTR included 22 patients who developed TR and 18 who had NP. The 15-year overall survival rate was 85.9% for patients with NP and 95.5% for those with TR, while it was 96.5% for patients without IBTR. Patients with high XRCC4 expression in tumor cells had significantly higher IBTR rates than those with low XRCC4 expression (P < 0.001). The frequency of TR was significantly higher in patients with high expression of XRCC4 than in those with low XRCC4 expression (p < 0.001). XRCC4 expression by tumor cells was not significantly related to development of NP. IBTR due to TR may be related to low radiosensitivity of tumor cells, possibly related to high XRCC4 expression.
Sections du résumé
BACKGROUND
BACKGROUND
We examined the expression of nonhomologous end-joining (NHEJ) proteins by breast cancer cells in patients with or without ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy. We also investigated whether there was a difference of NHEJ-related protein expression by tumor cells between two types of IBTR, i.e., true recurrence (TR) with regrowth from the tumor bed or development of a new primary tumor (NP).
PATIENTS AND METHODS
METHODS
The original cohort comprised 560 breast cancer patients who received breast-conserving therapy between February 1995 and March 2006, including 520 patients without IBTR and 40 patients with IBTR. Propensity score matching was employed to select 40 trios (120 patients) consisting of 1 patient with IBTR and 2 patients without IBTR. Immunohistochemical examination of proteins related to NHEJ was performed in surgical specimens.
RESULTS
RESULTS
The 40 patients with IBTR included 22 patients who developed TR and 18 who had NP. The 15-year overall survival rate was 85.9% for patients with NP and 95.5% for those with TR, while it was 96.5% for patients without IBTR. Patients with high XRCC4 expression in tumor cells had significantly higher IBTR rates than those with low XRCC4 expression (P < 0.001). The frequency of TR was significantly higher in patients with high expression of XRCC4 than in those with low XRCC4 expression (p < 0.001). XRCC4 expression by tumor cells was not significantly related to development of NP.
CONCLUSION
CONCLUSIONS
IBTR due to TR may be related to low radiosensitivity of tumor cells, possibly related to high XRCC4 expression.
Identifiants
pubmed: 30997540
doi: 10.1007/s00066-019-01468-z
pii: 10.1007/s00066-019-01468-z
doi:
Substances chimiques
DNA-Binding Proteins
0
XRCC4 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
648-658Références
Mutat Res. 1999 Jan 26;433(1):53-8
pubmed: 10047779
Int J Radiat Oncol Biol Phys. 2001 Jan 1;49(1):161-7
pubmed: 11163510
Lancet Oncol. 2002 Mar;3(3):183-7
pubmed: 11905457
Am J Clin Pathol. 2003 Oct;120(4):485-8
pubmed: 14560560
J Clin Oncol. 2006 May 1;24(13):2028-37
pubmed: 16648502
Mol Cell Biol. 2007 May;27(10):3793-803
pubmed: 17353262
Breast Cancer. 2009;16(1):49-57
pubmed: 18841332
Breast J. 2010 Mar-Apr;16(2):127-33
pubmed: 20030655
J Radiat Res. 2010;51(3):303-13
pubmed: 20448413
Int J Oncol. 2010 Dec;37(6):1547-54
pubmed: 21042724
Int J Radiat Oncol Biol Phys. 2011 Oct 1;81(2):409-17
pubmed: 21288654
Genes Dev. 2011 Mar 1;25(5):409-33
pubmed: 21363960
DNA Repair (Amst). 2011 Dec 10;10(12):1232-42
pubmed: 21982441
Lancet. 2011 Nov 12;378(9804):1707-16
pubmed: 22019144
Breast. 2012 Jun;21(3):230-6
pubmed: 22225710
Cancer. 2012 Sep 15;118(18):4385-93
pubmed: 22252882
Semin Radiat Oncol. 2012 Apr;22(2):100-7
pubmed: 22385917
Oncol Lett. 2012 Jul;4(1):151-155
pubmed: 22807979
Bone Marrow Transplant. 2013 Mar;48(3):452-8
pubmed: 23208313
Int J Radiat Oncol Biol Phys. 2014 Aug 1;89(5):1006-1014
pubmed: 25035203
J Cell Death. 2014 Feb 13;7:11-3
pubmed: 25278782
Med Mol Morphol. 2016 Dec;49(4):210-216
pubmed: 26867665
Med Mol Morphol. 2017 Mar;50(1):25-33
pubmed: 27338590
Sci Signal. 2017 Jul 18;10(488):null
pubmed: 28720717
J Clin Oncol. 2017 Oct 1;35(28):3222-3229
pubmed: 28759347
J Natl Cancer Inst. 1995 Jan 4;87(1):19-27
pubmed: 7666458
Cell. 1995 Dec 29;83(7):1079-89
pubmed: 8548796
Radiat Res. 1998 Nov;150(5 Suppl):S80-91
pubmed: 9806611