Table 1 Sample Description
Supplementary Table 1. Ten-year disease free survival rates according to clinicopathologic factors biomolecular markers and adjuvant treatment related variables in primary breast tumors (n=533 patients with stage I, II or III disease and disease free interval greater than 3 months).
Variable / Category / 10-year disease free survival (cumulative survival rate - %) / HR / 95% CI (HR)n / % / P
Age (years old) / < 40 / 70 / 40.8 / 0.005 / 1.0 / Reference
40 – 59 / 377 / 55.6 / 0.6 / 0.4 – 0.9
≥ 60 / 85 / 66.6 / 0.5 / 0.3 – 0.8
Hormonal status / Premenopause / 206 / 50.7 / 0.094 / 1.0 / Reference
Postmenopause / 326 / 57.6 / 0.8 / 0.6 – 1.0
Stage / Stage I / 36 / 78.4 / < 0.001 / 1.0 / Reference
Stage II / 251 / 70.5 / 1.5 / 0.7 – 3.2
Stage III / 245 / 35.5 / 4.5 / 2.1 – 9.5
Tumor size (cm) / ≤ 2.0 / 98 / 74.4 / < 0.001 / 1.0 / Reference
2.1 – 5.0 / 299 / 56.9 / 2.0 / 1.3 – 3.1
> 5.0 / 116 / 38.6 / 3.8 / 2.4 -6.2
Lymph node metastasis / No / 188 / 72.2 / < 0.001 / 1.0 / Reference
Yes / 337 / 46.3 / 2.7 / 1.9 – 3.7
Nuclear grade / Grade 1 / 6 / 75.0 / 0.275 / 1.0 / Reference
Grade 2 / 171 / 57.6 / 2.6 / 0.4 – 18.7
Grade 3 / 353 / 54.0 / 3.1 / 0.4 – 22.0
Scarff-Bloom- / Grade 1 / 67 / 67.9 / < 0.001 / 1.0 / Reference
Richardson / Grade 2 / 308 / 58.1 / 1.6 / 0.9 – 2.6
Grade 3 / 155 / 44.6 / 2.5 / 1.5 – 4.2
Estrogen receptor / Negative / 171 / 46.3 / < 0.001 / 1.7 / 1.3 – 2.2
Positive / 361 / 59.2 / 1.0 / Reference
Progesterone receptor / Negative / 277 / 48.5 / < 0.001 / 1.7 / 1.3 – 2.2
Positive / 255 / 62.1 / 1,0 / Reference
HER2 / Negative / 439 / 56.8 / 0.006 / 1.0 / Reference
Positive / 93 / 46.5 / 1.6 / 1.1 – 2.2
NDRG1 expression / Negative (≤ 80) / 304 / 67.2 / < 0.001 / 1.0 / Reference
(ACIS) / Positive (> 80) / 228 / 37.8 / 2.7 / 2.1 – 3.6
SPARC expression / Negative (≤ 110) / 146 / 42.9 / 0.001 / 1.6 / 1.2 – 2.1
(ACIS) / Positive (> 110) / 386 / 59.7 / 1.0 / Reference
NDRG1 / SPARC / NDRG1-/SPARC+ / 215 / 74.7 / < 0.001 / 1.0 / Reference
interaction / NDRG1-/SPARC- / 89 / 49.8 / 2.3 / 1.5 – 3.6
NDRG1+/SPARC+ / 171 / 40.1 / 3.5 / 2.4 – 5.0
NDRG1+/SPARC- / 57 / 31.2 / 4.7 / 3.0 – 7.2
Luminal A / No / 191 / 46.4 / < 0.001 / 1.7 / 1.3 – 2.2
Yes / 341 / 59.8 / 1.0 / Reference
Luminal B / No / 497 / 55.5 / 0.176 / 0.7 / 0.4 – 1.2
Yes / 35 / 46.8 / 1.0 / Reference
HER2 over-expression / No / 474 / 55.9 / 0.023 / 1.0 / Reference
Yes / 58 / 46.1 / 1.6 / 1.1 – 2.4
Triple negative / No / 434 / 56.9 / 0.024 / 1.0 / Reference
Yes / 98 / 46.8 / 1.5 / 1.1 – 2.0
Hormonal therapy / No / 227 / 51.3 / 0.076 / 1.0 / Reference
Yes / 205 / 56.2 / 0.8 / 0.6 – 1.0
Adjuvant chemotherapy / No / 166 / 53.3 / 0.557 / 1.0 / Reference
Yes / 266 / 54.1 / 1.1 / 0.8 – 1.5
Adjuvant radiotherapy / No / 59 / 49.0 / 0.211 / 1.0 / Reference
Yes / 373 / 54.5 / 0.7 / 0.5 – 1.2
PP value from log-rank test
HRHazard ratio
95% CI95% confidence interval
Supplementary Table 2. Ten-year overall survival rates according to NDRG1 and SPARC expressions and immunophenotypic groups in primary breast tumors (n=596 patients).
Immunophenotypic group / Biomolecular markers / 10-year overall survival (cumulative survival rate - %) / HR / 95% CI (HR)n / % / P
Luminal A / NDRG1 – negative (≤ 80) / 213 / 73.1 / < 0.001 / 1.0 / Reference
(n=374) / NDRG1 – positive (>80) / 147 / 38.0 / 3.5 / 2.4 – 5.0
SPARC–negative (≤ 110) / 119 / 44.3 / < 0.001 / 1.8 / 1.3 – 2.6
SPARC– positive (> 110) / 241 / 67.2 / 1.0 / Reference
Luminal B / NDRG1 – negative (≤ 80) / 17 / 74.5 / 0.003 / 1.0 / Reference
(40) / NDRG1 – positive (>80) / 22 / 34.6 / 4.6 / 1.5 – 14.3
SPARC–negative (≤ 110) / 8 / 25.0 / 0.063 / 2.5 / 0.9 – 6.5
SPARC– positive (> 110) / 31 / 60.4 / 1.0 / Reference
HER2 / NDRG1 – negative (≤ 80) / 35 / 53.8 / 0.061 / 1.0 / Reference
superexpression / NDRG1 – positive (>80) / 32 / 29.4 / 1.8 / 1.0 – 3.6
(n=67)
SPARC–negative (≤ 110) / 11 / 24.2 / 0.750 / 1.1 / 0.5 – 2.5
SPARC– positive (> 110) / 56 / 46.5 / 1.0 / Reference
Triple negative / NDRG1 – negative (≤ 80) / 52 / 49.0 / 0.013 / 1.0 / Reference
(n=115) / NDRG1 – positive (>80) / 61 / 33.1 / 1.9 / 1.1 – 3.2
SPARC–negative (≤ 110) / 26 / 17.1 / 0.004 / 2.1 / 1.2 – 3.6
SPARC– positive (> 110) / 87 / 48.5 / 1.0 / Reference
PP value from log-rank test
HRHazard ratio
95% CI95% confidence interval
Supplementary Table 3. Ten-year disease free survival rates according to NDRG1 and SPARC expressions and immunophenotypic groups in primary breast tumors (n=533 patients with stage I, II or III disease and disease free interval greater than 3 months).
Immunophenotypic group / Biomolecular markers / 10-year disease free survival (cumulative survival rate - %) / HR / 95% CI (HR)n / % / P
Luminal A / NDRG1 – negative (≤ 80) / 209 / 73.5 / < 0.001 / 1.0 / Reference
(n=341) / NDRG1 – positive (>80) / 132 / 37.4 / 3.5 / 2.5 – 5.1
SPARC–negative (≤ 110) / 111 / 47.9 / 0.002 / 1.8 / 1.2 – 2.5
SPARC– positive (> 110) / 230 / 65.6 / 1.0 / Reference
Luminal B / NDRG1 – negative (≤ 80) / 17 / 59.7 / 0.042 / 1.0 / Reference
(n=35) / NDRG1 – positive (>80) / 18 / 37.0 / 2.7 / 1.0 – 7.5
SPARC–negative (≤ 110) / 7 / 28.6 / 0.086 / 2.4 / 0.8 – 6.9
SPARC– positive (> 110) / 28 / 51.5 / 1.0 / Reference
HER2 / NDRG1 – negative (≤ 80) / 30 / 65.7 / 0.048 / 1.0 / Reference
superexpression / NDRG1 – positive (>80) / 28 / 28.4 / 2.1 / 1.0 – 4.6
(n=59)
SPARC–negative (≤ 110) / 8 / 42.9 / 0.882 / 0.9 / 0.3 – 2.7
SPARC– positive (> 110) / 50 / 46.9 / 1.0 / Reference
Triple negative / NDRG1 – negative (≤ 80) / 48 / 47.1 / 0.256 / 1.0 / Reference
(n=98) / NDRG1 – positive (>80) / 50 / 47.4 / 1.4 / 0.8 – 2.5
SPARC–negative (≤ 110) / 20 / 19.4 / 0.004 / 2.4 / 1.3 – 4.4
SPARC– positive (> 110) / 78 / 54.2 / 1.0 / Reference
PP value from log-rank test
HRHazard ratio
95% CI95% confidence interval
Supplementary Table 4. Number and percentages of patients according to NDRG1 and SPARC expressions and adjuvant treatment related variables (hormone therapy, adjuvant chemotherapy and adjuvant radiotherapy).
NDRG1 expression / P value (*) / SPARC expression / P value (*)Variable / Category / Negative (≤ 80) / Positive (> 80) / Negative (≤ 110) / Negative (≤ 110)
n (%) / n (%) / n (%) / n (%)
Hormone therapy / No / 123 (47.9) / 134 (52.1) / 0.001 / 72 (28.0) / 185 (72.0) / 0.183
Yes / 139 (62.3) / 84 (37.7) / 75 (33.6) / 148 (66.4)
Adjuvant chemotherapy / No / 97 (52.4) / 88 (47.6) / 0.300 / 58 (31.4) / 127 (68.6) / 0.731
Yes / 165 (57.3) / 123 (42.7) / 86 (29.9) / 202 (70.1)
Adjuvant radiotherapy / No / 32 (41.0) / 46 (59.0) / 0.009 / 31 (39.7) / 47 (60.3) / 0.056
Yes / 230 (57.2) / 172 (42.8) / 116 (28.9) / 286 (71.1)
(*) Chi square test
Supplementary Table 5. Risk factors for recurrence according to Cox proportional hazard model(*).
Variable / Categories / n / HR / 95% CI / P valueNDRG1 / Negative (≤ 80) / 247 / 1.0 / Reference / -
Positive (> 80) / 185 / 2.2 / 1.7 – 3.0 / < 0.001
SPARC / Negative (≤ 110) / 129 / 1.6 / 1.1 – 2.1 / 0.005
Positive (> 110) / 303 / 1.0 / Reference / -
Stage / Stage I / 27 / 1.0 / Reference / -
Stage II / 195 / 1.2 / 0.5 – 3.0 / 0.743
Stage III / 210 / 3.2 / 1.3 – 8.1 / 0.013
Estrogen receptor / Negative / 141 / 1.3 / 0.9 – 1.9 / 0.173
Positive / 291 / 1.0 / Reference / -
Progesterone receptor / Negative / 233 / 1.4 / 1.0 – 1.9 / 0.092
Positive / 199 / 1.0 / Reference / -
HER2 / Negative / 355 / 1.0 / Reference / -
Positive / 77 / 1.1 / 0.8 – 1.6 / 0.566
Hormonal therapy / No / 227 / 1.0 / Reference / -
Yes / 205 / 1.1 / 0.8 – 1.5 / 0.733
Adjuvant chemotherapy / No / 166 / 1.0 / Reference / -
Yes / 266 / 1.0 / 0.7 – 1.4 / 0.969
Adjuvant radiotherapy / No / 59 / 1.0 / Reference / -
Yes / 373 / 0.6 / 0.4 – 0.9 / 0.013
Age / (continuous variable) / 432 / 0.99 / 0.98 – 1.00 / 0.255
(*)Number of patients = 432 (stage I, II or III disease and disease-free interval greater than 3 months)
Number of events (recurrences) = 181
Number of cases with missing values = 101
HRHazard ratio
95% CI95% confidence interval