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. 2019 Dec 10;14(12):e0226150. doi: 10.1371/journal.pone.0226150

Table 1. Patient and tumor characteristics in relation to HIF and EGFR-status of both tumors.

N = 688 First breast cancer, N (%) Second breast cancer, N (%)
HIF1/EGFR missing for 97/88 BC1, 54/52 BC2 HIF1-negative HIF1-positive P-valuea EGFR-negative EGFR-positive P-valuea HIF1-negative HIF1-positive P-valuea EGFR-negative EGFR-positive P-valuea
N = 522 (88%) N = 69 (12%) N = 520 (87%) N = 80 (13%) N = 523 (82%) N = 111 (18%) N = 570 (90%) N = 66
(10%)
Date of diagnosis 0.6 0.001 0.2 0.9
<1977 82 (92%) 7 (8%) 68 (75%) 23 (25%) 0 0 0 0
1977–1986 158 (87%) 23 (13%) 159 (87%) 24 (13%) 102 (86%) 16 (14%) 107 (90%) 12 (10%)
1987–1996 204 (87%) 30 (13%) 214 (90%) 25 (10%) 181 (82%) 39 (18%) 199 (90%) 23 (10%)
1997–2007 78 (90%) 9 (10%) 79 (91%) 8 (9%) 240 (81%) 56 (19%) 264 (89%) 31 (11%)
Age at diagnosis 0.009 <0.001 0.03 <0.001
<50 years 140 (83%) 29 (17%) 139 (79%) 37 (21%) 52 (73%) 19 (27%) 54 (76%) 17 (24%)
≥50 years 382 (91%) 40 (9%) 381 (90%) 43 (10%) 471 (84%) 92 (16%) 516 (91%) 49 (9%)
Node status 0.9 0.04 0.002 0.5
N0 323 (88%) 43 (12%) 317 (85%) 57 (15%) 289 (85) 51 (15%) 304 (90%) 35 (10%)
N+ 165 (88%) 23 (12%) 172 (91%) 17 (9%) 141 (74) 49 (26%) 167 (88%) 23 (12%)
If N+ Median (range) 3 (1–33) 2 (1–12) 2.5 (1–33) 2.5 (1–10)
2 (1–23) 2 (1–21) 2 (1–23) 4 (1–11)
Missing 34 3 31 6 93 11 99 8
Size 0.4 0.6 0.7 0.01
≤20 mm 312 (89%) 38 (11%) 314 (88%) 43 (12%) 366 (83%) 75 (17%) 406 (91%) 38 (9%)
>20 mm 177 (87%) 27 (13%) 176 (86%) 28 (14%) 143 (82%) 32 (18%) 147 (84%) 27 (16%)
Median (range) 18 (1–100) 20 (1–70) 17 (1–100) 20 (1–70) 15 (1–110) 17 (1–80) 15 (1–110) 20 (1–80)
Missing 33 4 30 9 14 4 17 1
Stage 0.4 0.3 0.008 0.1
I 233 (89%) 29 (11%) 232 (87%) 36 (13%) 234 (86%) 39 (14%) 247 (90%) 26 (10%)
II 163 (88%) 22 (12%) 162 (87%) 24 (13%) 123 (77%) 36 (23%) 142 (90%) 16 (10%)
III 55 (85%) 10 (15%) 60 (92%) 5 (8%) 62 (75%) 21 (25%) 69 (83%) 14 (17%)
Missing 71 8 66 15 104 15 112 10
ER-status <0.001 <0.001 <0.001 <0.001
<10% 75 (76%) 24 (24%) 49 (51%) 48 (49%) 54 (52%) 50 (48%) 54 (52%) 50 (48%)
≥10% 442 (91%) 44 (9%) 464 (94%) 29 (6%) 463 (89%) 57 (11%) 507 (97%) 14 (3%)
Missing 5 1 7 3 6 4 9 2
PR-status <0.001 <0.001 <0.001 <0.001
<10% 132 (80%) 33 (20%) 110 (67%) 53 (43%) 145 (69%) 65 (31%) 158 (75%) 52 (25%)
≥10% 385 (92%) 35 (8%) 403 (94%) 24 (6%) 367 (90%) 42 (10%) 399 (97%) 11 (3%)
Missing 5 1 7 3 11 4 13 3
HER2-status 0.005 0.07 <0.001 0.07
Negative (0 to 2+) 482 (90%) 56 (10%) 476 (88%) 68 (13%) 495 (85%) 85 (15%) 526 (90%) 56 (10%)
Positive (3+) 30 (75%) 10 (25%) 31 (78%) 9 (23%) 18 (49%) 19 (51%) 30 (81%) 7 (19%)
Missing 10 3 13 3 10 7 14 3
Ki67 <0.001 <0.001 <0.001 <0.001
≤20 440 (93%) 34 (7%) 440 (92%) 39 (8%) 442 (90%) 51 (10%) 469 (95%) 26 (5%)
>20 72 (69%) 32 (31%) 67 (64%) 37 (36%) 65 (55%) 53 (45%) 82 (69%) 36 (31%)
Missing 10 3 13 4 16 7 19 4
EGFR <0.001 <0.001
Negative 467 (91%) 45 (9%) - - 493 (87%) 73 (13%) - -
Positive 54 (70%) 23 (30%) - - 29 (44%) 37 (56%) - -
Missing 1 1 1 1
Subtype <0.001 <0.001 <0.001 <0.001
Luminal A-like 330 (93%) 23 (7%) 338 (94%) 20 (6%) 314 (94%) 21 (6%) 331 (98%) 6 (2%)
Luminal B-like HER2- 97 (87%) 15 (13%) 105 (94%) 7 (6%) 127 (84%) 25 (16%) 147 (97%) 5 (3%)
Luminal B-like HER2+ 12 (71%) 5 (29%) 16 (94%) 1 (6%) 10 (53%) 9 (47%) 17 (89%) 2 (11%)
HER2+ 16 (76%) 5 (24%) 13 (62%) 8 (38%) 7 (44%) 9 (56%) 11 (69%) 5 (31%)
Triple Negative 45 (71%) 18 (29%) 24 (38%) 39 (62%) 38 (51%) 37 (49%) 32 (43%) 43 (57%)
Missing 22 3 24 5 27 10 32 5
Time-interval BC1-BC2 0.04 0.8 0.2 0.1
<5 year 226 (85%) 39 (15%) 231(86%) 37 (14%) 215 (80%) 53 (20%) 235 (87%) 34 (13%)
≥5 years 296 (91%) 30 (9%) 289 (87%) 43 (13%) 308 (84%) 58 (16%) 335 (91%) 32 (9%)

Abbreviations: BC1 first breast cancer BC2 second breast cancer, EGFR Epidermial growth factor receptor, ER estrogen receptor, HIF Hypoxia-inducible factor, N+ lymph-node metastases, N0 no lymph-node metastases, N number, node status lymph-node status, PR progesterone receptor.

a χ2-test except for date of diagnosis and stage where a χ2-test for trend was used.