Background
Methods
Adjuvant systemic therapy
Data collection
GUH | CMSE Namur | |||
---|---|---|---|---|
(n = 282) | (n = 95) | |||
Age (years) | ||||
Median | 57.5 | 59.0 | ||
Range | 30-82 | 35-82 | ||
Bra cup size | ||||
Small | A | 13 (4.6) | 3 (3.2) | |
B | 85 (30.2) | 33 (34.7) | ||
C | 101 (35.8) | 34 (35.8) | ||
Large | D | 53 (18.8) | 16 (16.8) | |
E | 16 (5.7) | 5 (5.3) | ||
F | 7 (2.5) | 3 (3.2) | ||
G + H | 2 (0.6) | 1 (1.0) | ||
Missing
|
5
|
0
| ||
BMI | ||||
Median | 25.5 | 26 | ||
Range | 16-50 | 16-38 | ||
Missing
| 2 | 0 | ||
Menstruation | ||||
No | 235 (83.3) | 76 (80.0) | ||
Yes | 45 (16.0) | 18 (18.9) | ||
Missing
|
2
|
1
| ||
Smoking during RT | ||||
No | 244 (86.5) | 79 (83.2) | ||
Yes | 35 (12.4) | 16 (16.8) | ||
Missing
|
3
|
0
| ||
Diabetes | ||||
No | 254 (90.1) | 84 (88.4) | ||
Yes | 22 (7.8) | 11 (11.6) | ||
Missing
|
6
|
0
| ||
Hypertension | ||||
No | 196 (69.5) | 66 (69.5) | ||
Yes | 81 (28.7) | 29 (30.5) | ||
Missing
|
5
|
0
| ||
Fractionation | ||||
Normo | 0 | 45 (47.4) | ||
Hypo | 282 | 50 (52.6) | ||
Missing
|
0
|
0
| ||
Treatment position | ||||
Supine | 195 (69.1) | 95 (100.0) | ||
Prone | 87 (30.9) | 0 | ||
Missing
|
0
|
0
| ||
Boost | ||||
No | 64 (22.7) | 7 (7.4) | ||
Yes | 218 (77.3) | 88 (92.6) | ||
Missing
|
0
|
0
| ||
Nodal irradiation | ||||
No | 241 (85.5) | 87 (80.6) | ||
Yes | 41 (14.5) | 21 (19.4) | ||
Missing
|
0
|
0
| ||
Hormonal therapy | ||||
No | 46 (16.3) | 25 (26.3) | ||
Concomitant | 236 (83.7) | 7 (7.4) | ||
Sequential (after IMRT) | 0 | 63 (66.3) | ||
Missing
|
0
|
0
| ||
Chemotherapy | ||||
No | 188 (66.7) | 55 (57.9) | ||
Yes | 94 (33.3) | 40 (42.1) | ||
Missing
|
0
|
0
| ||
Trastuzumab | ||||
No | 257 (91.1) | 83 (87.4) | ||
Yes | 25 (8.9) | 12 (12.6) | ||
Missing
|
0
|
0
|
Selection of candidate genes/polymorphisms and genotyping
Gene or gene regulator | rs number | MAF* | Nucleotide substitution | Genomic location | Amino acid substitution | Reference |
---|---|---|---|---|---|---|
LIG3
| rs3744355 | 9.1 | G > C | 5′-flanking | - | |
MLH1
| rs1800734 | 22.6 | G > A | 5′-UTR | - | [14] |
XRCC3
| rs861539 | 39.0 | C > T | Coding | Thr241Met | [15] |
PHLDA3
| rs3888929 | 30.3 | G > A | Unknown | - | [16] |
LCP2
| rs4867592 | 19.1 | C > A | Unknown | - | [16] |
LTHA4
| rs7970524 | 25.1 | T > C | 5′-flanking | - | [16] |
NDUFB6
| rs12003093 | 23.4 | A > G | Unknown | - | [16] |
VDR
| rs4760658 | 36.6 | A > G | Intronic | - | [16] |
Statistical analysis
Results
Acute radiation-induced skin toxicity
All (n = 377) | G0-1 (n = 157) | G2+ (n = 220) | p-value | pBH-value | ||
---|---|---|---|---|---|---|
Bra cup size | ||||||
A + B + C | 269 (71.4) | 130 (48.3) | 139 (51.7) | |||
≥D | 103 (27.3) | 26 (25.2) | 77 (74.8) |
<0.001
|
0.001
| |
BMI | ||||||
Median | 26 | 24 | 26 | |||
Range | 16-50 | 16-37 | 16-50 |
<0.001
|
0.001
| |
Smoking during RT | ||||||
No | 323 (85.7) | 141 (43.7) | 182 (56.3) | |||
Yes | 51 (13.5) | 14 (27.5) | 37 (72.5) |
0.029
| 0.156 | |
Fractionation | ||||||
Normo | 45 (11.9) | 6 (13.3) | 39 (86.7) | |||
Hypo | 332 (88.1) | 151 (45.5) | 181 (54.5) |
<0.001
|
<0.001
| |
Treatment position | ||||||
Supine | 290 (76.9) | 108 (37.2) | 182 (62.8) | |||
Prone | 87 (23.1) | 49 (56.3) | 38 (43.7) |
0.002
|
0.019
| |
Nodal irradiation | ||||||
No | 315 (83.6) | 141 (44.8) | 174 (55.2) | |||
Yes | 62 (16.4) | 16 (25.8) | 46 (74.2) |
0.006
|
0.037
| |
Hormonal therapy | ||||||
No | 71 (18.8) | 39 (54.9) | 32 (45.1) | |||
Concomitant | 243 (64.5) | 94 (38.7) | 149 (61.3) | |||
Sequential (after IMRT) | 63 (16.7) | 24 (38.1) | 39 (61.9) |
0.041
| 0.207 | |
Hormones (concomitant)
| ||||||
Tamoxifen
|
155
|
62 (40.0)
|
93 (60.0)
| |||
Aromatase inhibitor
|
85
|
32 (37.6)
|
53 (62.4)
| |||
Chemotherapy | ||||||
No | 243 (64.5) | 92 (37.9) | 151 (62.1) | |||
Yes | 134 (35.5) | 65 (48.5) | 69 (51.5) |
0.045
| 0.215 | |
Trastuzumab | ||||||
No | 340 (90.2) | 133 (39.1) | 207 (60.9) | |||
Yes | 37 (9.8) | 24 (64.9) | 13 (35.1) |
0.003
|
0.026
|
Clinical/genetic factor | Acute G2+ dermatitis | Moist desquamation | ||
---|---|---|---|---|
OR | p-value | OR | p-value | |
Center (CMSE vs. GUH) | - | - | 3.206 | 0.158 |
BMI
|
1.088
|
0.003
|
1.170
|
<0.001
|
Bra cup size (cup ≥ D vs. cup A + B + C) |
2.833
|
0.001
|
2.146
|
0.043
|
Smoking (yes vs. no) |
2.711
|
0.010
|
-
|
-
|
Fractionation (hypo vs. normo) |
0.083
|
<0.001
|
0.096
|
<0.001
|
Treatment position (prone vs. supine) |
0.399
|
0.004
| 0.373 | 0.074 |
Hormone therapy
| ||||
No | 1 | 1 | ||
Concomitant |
3.207
|
0.001
|
4.770
|
0.037
|
Sequential (after IMRT) | 1.003 | 0.994 | 1.078 | 0.901 |
Nodal irradiation (yes vs. no) | 1.975 | 0.100 | - | - |
Chemotherapy (yes vs. no) | 0.954 | 0.877 | - | - |
Trastuzumab (yes vs. no) |
0.177
|
<0.001
| - | - |
MLH1
rs1800734 G > A
| ||||
GG | 1 | - | ||
GA |
0.492
|
0.008
| - | - |
AA | 0.537 | 0.232 | - | - |
All patients | ||||||
---|---|---|---|---|---|---|
All (n = 377) | No (n = 321) | Yes (n = 56) | p-value | pBH-value | ||
Bra cup size | ||||||
A + B + C | 269 (71.4) | 242 (90.0) | 27 (10.0) | |||
≥D | 103 (27.3) | 76 (73.8) | 27 (26.2) |
<0.001
|
0.001
| |
BMI | ||||||
Median | 26 | 25 | 29 | |||
Range | 16-50 | 16-40 | 21-50 |
<0.001
|
<0.001
| |
Fractionation | ||||||
Normo | 45 (11.9) | 22 (48.9) | 23 (51.1) | |||
Hypo | 332 (88.1) | 299 (90.1) | 33 (9.9) |
<0.001
|
<0.001
| |
Treatment position | ||||||
Supine | 290 (76.9) | 239 (82.4) | 51 (17.6) | |||
Prone | 87 (23.1) | 82 (94.3) | 5 (5.7) |
0.002
|
0.019
| |
Hormonal therapy | ||||||
No | 71 (18.8) | 62 (87.3) | 9 (12.7) | |||
Concomitant | 243 (64.5) | 214 (88.1) | 29 (11.9) | |||
Sequential (after IMRT) | 63 (16.7) | 45 (71.4) | 18 (28.6) |
0.004
|
0.029
| |
Hormones (concomitant)
| ||||||
Tamoxifen
|
155
|
139 (89.7)
|
16 (10.3)
| |||
Aromatase inhibitor
|
85
|
74 (87.1)
|
11 (12.9)
|
Acute G2+ dermatitis | Moist desquamation | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
G0-1 (n = 157) | G2+ (n = 220) | OR | p-value | pBH-value | No (n = 321) | Yes (n = 95) | OR | p-value | pBH-value | ||
MLH1
rs1800734
| |||||||||||
G > A | GG | 81 (51.6) | 146 (66.4) | 189 (58.9) | 38 (67.9) | ||||||
GA | 64 (40.8) | 60 (27.3) | 0.52 |
0.004
|
0.029
| 110 (34.3) | 14 (25.0) | 0.63 | 0.172 | 0.477 | |
AA | 9 (5.7) | 12 (5.5) | 0.74 | 0.514 | 0.804 | 17 (5.3) | 4 (7.1) | 1.17 | 0.788 | 0.915 | |
Missing
|
3 (1.9)
|
2 (0.9)
|
5 (1.6)
|
0
| |||||||
GG vs. GA + AA (dominant) | 0.55 |
0.005
|
0.033
| 0.71 | 0.257 | 0.575 | |||||
GG + GA vs. AA (recessive) | 0.94 | 0.889 | 0.936 | 1.35 | 0.600 | 0.860 |