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Prognostic significance of uPA/PAI-1 level, HER2 status, and traditional histologic factors for survival in node-negative breast cancer patients

Nina Fokter Dovnik
Nina Fokter Dovnik
 und 
Iztok Takac
Iztok Takac
   | 07. Feb. 2016
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Article Category: Research Article
Online veröffentlicht: 07. Feb. 2016
Seitenbereich: 65 - 73
Eingereicht: 13. Dez. 2015
Akzeptiert: 03. Apr. 2016
DOI: https://doi.org/10.1515/raon-2016-0024
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© 2017 Nina Fokter Dovnik, Iztok Takac
This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Effect of uPA/PAI-1 level and HER2 status on disease-free survival (DFS) in lymph-node negative breast cancer patients. (A) uPA/PAI-1 low (19 of 159 relapsed or died) versus uPA/PAI-1 high (43 of 173 relapsed or died). (B) HER2 negative (154 of 610 relapsed or died) versus HER2 positive not treated with adjuvant trastuzumab (NT) (37 of 97 relapsed or died) and HER2 positive treated with adjuvant trastuzumab (T) (8 of 54 relapsed or died).NT = not treated with adjuvant trastuzumab; T = treated with adjuvant trastuzumab
Effect of uPA/PAI-1 level and HER2 status on disease-free survival (DFS) in lymph-node negative breast cancer patients. (A) uPA/PAI-1 low (19 of 159 relapsed or died) versus uPA/PAI-1 high (43 of 173 relapsed or died). (B) HER2 negative (154 of 610 relapsed or died) versus HER2 positive not treated with adjuvant trastuzumab (NT) (37 of 97 relapsed or died) and HER2 positive treated with adjuvant trastuzumab (T) (8 of 54 relapsed or died).NT = not treated with adjuvant trastuzumab; T = treated with adjuvant trastuzumab

Effect of uPA/PAI-1 level and HER2 status on overall survival (OS) in lymph-node negative breast cancer patients. (A) uPA/PAI-1 low (10 of 159 died) versus uPA/PAI-1 high (31 of 173 died). (B) HER2 negative (118 of 610 died) versus HER2 positive not treated with adjuvant trastuzumab (26 of 97 died) and HER2 positive treated with adjuvant trastuzumab (5 of 54 died).NT = not treated with adjuvant trastuzumab; T = treated with adjuvant trastuzumab
Effect of uPA/PAI-1 level and HER2 status on overall survival (OS) in lymph-node negative breast cancer patients. (A) uPA/PAI-1 low (10 of 159 died) versus uPA/PAI-1 high (31 of 173 died). (B) HER2 negative (118 of 610 died) versus HER2 positive not treated with adjuvant trastuzumab (26 of 97 died) and HER2 positive treated with adjuvant trastuzumab (5 of 54 died).NT = not treated with adjuvant trastuzumab; T = treated with adjuvant trastuzumab

Univariate and multivariate analysis of breast cancer specific survival in lymph node-negative breast cancer patients with a median follow-up time of 100 months. Multivariate analysis was performed in the 273 patients for whom complete data were available

Univariate analysisMultivariate analysis withall variablesMultivariate analysis –backward LR modelModel if term removed
hazard ratio (95 % CI)phazard ratio (95 % CI)phazard ratio (95 % CI)pp
Age(continuous, unit = 10 years)1.16(0.95–1.41)0.1480.76(0.51–1.12)0.162––0.160
Tumor size(≥2 vs. <2 cm)2.44(1.45–4.13)0.0011.72(0.55–5.38)0.350––0.340
Tumor type(other invasive vs. ductal invasive)1.20(0.63–2.29)0.5873.33(0.64–17.23)0.152––0.196
Grade(G3 vs. G1-2)3.58(2.12–6.05)< 0.0017.10(1.23–40.86)0.02810.34(2.33–45.97)0.0020.014
Lymphovascular invasion(present vs. absent)1.48(0.70–3.12)0.3051.43(0.36–5.65)0.608––0.618
Estrogen receptors(negative vs. positive)2.21(1.33–3.66)0.0021.24(0.28–5.36)0.778––0.776
Progesterone receptors(negative vs. positive)1.74(1.06–2.86)0.0280.81(0.17–3.77)0.789––0.788
HER2 status  0.031  0.663    0.614
positive NT vs. negative2.18(1.21–3.93)0.0091.29(0.39–4.31)0.683––  
positive T vs. negative0.96(0.30–3.10)0.9440.46(0.06–3.68)0.460––  
uPA/PAI-1(one or both high vs. both low)6.46(1.47–28.43)0.0142.79(0.57–13.67)0.205––0.166

j.raon-2016-0024.tab.003.w2aab3b8c39b1b7b1ab1b2b4b3Ab2

Univariate analysisMultivariate analysis withall variablesMultivariate analysis –backward LR modelModel if term removed
hazard ratio (95 % CI)phazard ratio (95 % CI)phazard ratio (95 % CI)pp
Age(continuous, unit = 10 years)2.18(1.88–2.52)< 0.0011.61(1.19–2.17)0.0021.68(1.25–2.27)0.0010.001
Tumor size(≥2 vs. <2 cm)1.38(1.02–1.88)0.0360.94(0.47–1.88)0.865––0.865
Tumor type(other invasive vs. ductal invasive)1.24(0.83–1.85)0.2982.24(0.76–6.59)0.142––0.165
Grade(G3 vs. G1-2)1.40(1.01–1.94)0.0422.39(0.95–6.02)0.0662.69(1.34–5.40)0.0050.064
Lymphovascular invasion(present vs. absent)1.34(0.83–2.16)0.2361.36(0.46–4.01)0.582––0.594
Estrogen receptors(negative vs. positive)1.24(0.88–1.75)0.2241.80(0.67–4.81)0.242––0.233
Progesterone receptors(negative vs. positive)1.01(0.74–1.38)0.9550.62(0.25–1.54)0.299––0.279
HER2 status  0.190  0.843    0.837
positive NT vs. negative1.37(0.89–2.09)0.1520.76(0.31–1.90)0.562––  
positive T vs. negative0.63(0.26–1.55)0.3180.90(0.26–3.18)0.871––  
uPA/PAI-1(one or both high vs. both low)2.73(1.33–5.58)0.0061.98(0.83–4.76)0.126––0.114

Univariate and multivariate analysis of disease–free survival in lymph node–negative breast cancer patients with a median follow–up time of 100 months. Multivariate analysis was performed in the 273 patients for whom complete data were available

Univariate analysisMultivariate analysis withall variablesMultivariate analysis –backward LR modelModel if term removed
hazard ratio (95 % CI)phazard ratio (95 % CI)phazard ratio (95 % CI)pp
Age(continuous, unit = 10 years)1.80(1.60–2.02)< 0.0011.53(1.20–1.96)0.0011.51(1.19–1.93)0.001< 0.001
Tumor size(≥2 vs. <2 cm)1.41(1.08–1.83)0.0121.01(0.56–1.80)0.982––0.982
Tumor type(other invasive vs. ductal invasive)1.08(0.76–1.55)0.6581.28(0.51–3.20)0.598––0.606
Grade(G3 vs. G1–2)1.37(1.03–1.81)0.0311.54(0.75–3.17)0.240––0.240
Lymphovascular invasion(present vs. absent)1.54(1.03–2.29)0.0351.43(0.65–3.15)0.377––0.393
Estrogen receptors(negative vs. positive)1.19(0.87–1.61)0.2711.81(0.79–4.16)0.1652.25(1.24–4.09)0.0080.158
Progesterone receptors(negative vs. positive)1.10(0.84–1.45)0.4961.03(0.48–2.23)0.935––0.935
HER2 status  0.005  0.355    0.379
positive NT vs. negative1.73(1.21–2.47)0.0031.66(0.83–3.31)0.150––  
positive T vs. negative0.70(0.35–1.43)0.3321.16(0.46–2.91)0.758––  
uPA/PAI–1(one or both high vs. both low)2.16(1.23–3.72)0.0051.76(0.89–3.49)0.1061.99(1.05–3.77)0.0350.098

Distribution of traditional prognostic factors, HER2 status, uPA and PAI-1 in the study group of node-negative breast cancer patients (N = 858)

FactorsNo. of patients%
Age858  
≥ 40 years82195.7
< 40 years374.3
Pathological tumor size846  
< 2 cm47456.0
≥ 2 cm37244.0
Pathological tumor type858  
Ductal invasive72083.9
Other invasive13816.1
Histological grade799  
G1-255769.7
G324230.3
Lymphovascular invasion795  
No72090.6
Yes759.4
Estrogen receptor status854  
Positive67478.9
Negative18021.1
Progesterone receptor status803  
Positive46658.0
Negative33742.0
HER2 status761  
Negative61080.2
Positive, without adjuvant trastuzumab9712.7
Positive, with adjuvant trastuzumab547.1
uPA and PAI-1 level332  
Both low15947.9
One or both high17352.1
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