Background
Methods
Study population
Chemotherapy regimen
Genotyping analysis
Statistical analysis
Results
Patient characteristics
Characteristics | No. of patients (%) |
---|---|
All patients | 244 (100) |
Median age, years (min-max) | 51.3 (26.6–75.6) |
Stage | |
I | 111 (45.5) |
II | 93 (38.1) |
III | 40 (16.4) |
Tumor size, ≤2 cm | 49 (34.0) |
Positive lymph nodes status | 107 (43.9) |
Tumor grade | |
G1 | 18 (7.4) |
G2 | 143 (58.6) |
G3 | 59 (24.2) |
Unknown | 24 (9.8) |
Histology | |
Ductal infiltrating carcinoma | 212 (86.9) |
Other histology | 32 (14.1) |
Positive ER status (cut-off > 10%) | 154 (63.1) |
Positive PgRstatus(cut-off > 10%) | 137 (56.1) |
Ki67 positive status(cut-off > 14%) | 112 (45.9) |
Positive p53 status(cut-off ≥ 1%) | 34 (13.9) |
Positive HER2a(IHC/FISH) | 26 (10.7) |
Surgery | |
Conservative | 201 (82.4) |
Mastectomy | 43 (17.6) |
Adjuvant chemotherapy | |
CMF | 124 (50.8) |
FEC | 120 (49.2) |
Endocrine therapy | 148 (60.6) |
Radiotherapy | 205 (84.0) |
Frequencies and associations among the polymorphisms and clinical-pathological features
Toxicity and effect of polymorphisms in whole BC group
HEMATOLOGIC TOXICITY | NON-HEMATOLOGIC TOXICITY | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
LEUCOPENIA | NEUTROPENIA | STOMATITIS | HEPATIC | |||||||||||||
Genotype | 0–1-2 | 3–4 | OR (95%CI) |
p
| 0–1-2 | 3–4 | OR (95%CI) |
P
| 0–1-2 | 3–4 | OR (95%CI) |
p
| 0–1-2 | 3–4 | OR (95%CI) |
p
|
GSTT1 | ||||||||||||||||
null | 47 | 3 | 1 (reference) | 0.155 | 45 | 5 | 1 (reference) | 0.349 | 49 | 1 | 1 (reference) | 0.822 | 49 | 1 | 1 (reference) | 0.335 |
Present | 190 | 4 | 0.33 (0.07–1.52) | 182 | 12 | 0.59 (0.30–1.77) | 191 | 3 | 0.77 (0.08–7.56) | 193 | 1 | 0.25(0.02–4.13) | ||||
GSTM1 | ||||||||||||||||
null | 129 | 3 | 1 (reference) | 0.548 | 122 | 10 | 1 (reference) | 131 | 1 | a | 132 | 0 | a | |||
Present | 108 | 4 | 1.59 (0.35–7.27) | 105 | 7 | 0.81 (0.30–2.21) | 0.686 | 109 | 3 | 110 | 2 | |||||
GSTP1 | ||||||||||||||||
AA | 141 | 4 | 1 (reference) | 0.832 | 134 | 11 | 1 (reference) | 0.150 | 142 | 3 | 1 (reference) | 0.569 | 144 | 1 | a | |
AG | 91 | 3 | 1.18 (0.26–5.39) | 89 | 5 | 0.70 (0.23–2.07) | 93 | 1 | 0.52 (0.05–5.04) | 93 | 1 | |||||
GG | 3 | 0 | 2 | 1 | 3 | 0 | 3 | 0 | ||||||||
RCF1 | ||||||||||||||||
GG | 71 | 3 | 1 (reference) | 0.598 | 69 | 5 | 1 (reference) | 0.759 | 73 | 1 | 1 (reference) | 0.824 | 74 | 0 | a | |
GA | 110 | 3 | 0.64 (0.13–3.29) | 104 | 9 | 1.19 (0.38–3.72) | 111 | 2 | 1.32 (0.12–14.8) | 113 | 0 | |||||
AA | 56 | 1 | 0.42 (0.04–4.17) | 0.461 | 54 | 3 | 0.77 (0.18–3.35) | 0.724 | 56 | 1 | 1.30 (0.08–21.3) | 0.852 | 55 | 2 | ||
AA vs. GA + GG | 0.54 (0.06–4.57) | 0.571 | 0.69 (0.19–2.48) | 0.566 | 1.10 (0.11–10.74) | 0.938 | ||||||||||
MTHFR | ||||||||||||||||
CC | 64 | 1 | 1 (reference) | 66 | 1 | 1 (reference) | 67 | 0 | a | 67 | 0 | a | ||||
CT | 113 | 3 | 0.57 (0.11–2.89) | 0.494 | 103 | 13 | 8.32 (1.06–65.2) | 0.043 | 114 | 2 | 115 | 1 | ||||
TT | 60 | 1 | 0.36 (0.04–3.51) | 0.376 | 58 | 3 | 3.41 (0.35–33.7) | 0.294 | 59 | 2 | 60 | 1 | ||||
TT vs. CT + CC | 0.49 (0.06–4.17) | 0.515 | 0.62 (0.17–2.25) | 0.472 | 3.07 (0.42–22.3) | 0.268 | ||||||||||
TS-TR | ||||||||||||||||
2R/2R | 84 | 2 | 1 (reference) | 83 | 3 | 1 (reference) | 85 | 1 | 1 (reference) | 86 | 0 | a | ||||
2R/3R | 74 | 4 | 0.44 (0.08–2.47) | 0.352 | 68 | 10 | 0.25 (0.06–0.93) | 0.038 | 76 | 2 | 0.45 (0.04–5.03) | 0.514 | 78 | 0 | ||
3R/3R | 79 | 1 | 0.23 (0.03–2.14) | 0.199 | 76 | 4 | 0.36 (0.11–1.19) | 0.095 | 79 | 1 | 0.48 (0.04–5.42) | 0.553 | 78 | 2 | ||
3/3R vs. 2/3R + 2/2R | 0.33 (0.04–2.82) | 0.313 | 0.61 (0.19–1.94) | 0.403 | 0.68 (0.07–6.64) | 0.740 |
Survival analysis
Univariate analysis - DFS | Univariate analysis - OS | |||||||
---|---|---|---|---|---|---|---|---|
Variable | HR | 95% CI |
p
| HR | 95% CI |
p
| ||
Age (per years) | 1.01 | 0.99 | 1.04 | 0.270 | 1.05 | 1.01 | 1.08 | 0.005 |
ER- PgR- | 1 (reference) | 1 (reference) | ||||||
ER+ PgR- / ER- PgR+ | 0.72 | 0.40 | 1.30 | 0.273 | 0.64 | 0.30 | 1.40 | 0.269 |
ER+ PgR+ | 0.51 | 0.29 | 0.89 | 0.018 | 0.51 | 0.25 | 1.04 | 0.066 |
Stage I | 1 (reference) | 1 (reference) | ||||||
Stage II | 2.01 | 1.13 | 3.56 | 0.018 | 3.73 | 1.48 | 9.41 | 0.005 |
Stage III | 3.77 | 2.01 | 7.08 | <0.001 | 9.77 | 3.85 | 24.82 | <0.001 |
LN (pos vs. neg) | 1.79 | 1.11 | 2.88 | 0.016 | 2.61 | 1.37 | 4.98 | 0.004 |
HER2 (pos vs. neg) | 1.51 | 0.75 | 3.04 | 0.251 | 1.67 | 0.70 | 3.97 | 0.248 |
GSTT1 (null vs. present) | 1.68 | 0.99 | 2.86 | 0.053 | 2.22 | 1.17 | 4.24 | 0.015 |
GSTM1 (present vs. null) | 1.23 | 0.77 | 1.98 | 0.383 | 1.68 | 0.90 | 3.12 | 0.103 |
RFC1 – AA | 1 (reference) | 1 (reference) | ||||||
RFC1 – GA | 2.35 | 1.09 | 5.07 | 0.029 | 1.95 | 0.73 | 5.22 | 0.184 |
RFC1 – GG | 2.89 | 1.31 | 6.38 | 0.009 | 2.90 | 1.07 | 7.88 | 0.036 |
GSTP1 – AA | 1 (reference) | 1 (reference) | ||||||
GSTP1 – AG | 0.77 | 0.46 | 1.26 | 0.297 | - | - | - | 0.989 |
GSTP1 – GG | - | - | - | 0.985 | 0.80 | 0.42 | 1.53 | 0.500 |
MTHFR – CC | 1 (reference) | 1 (reference) | ||||||
MTHFR – CT | 1.28 | 0.72 | 2.27 | 0.394 | 1.02 | 0.49 | 2.13 | 0.957 |
MTHFR – TT | 0.85 | 0.42 | 1.71 | 0.642 | 0.96 | 0.41 | 2.25 | 0.920 |
TS-TR – 2R/2R | 1 (reference) | 1 (reference) | ||||||
TS-TR – 2R/3R | 0.62 | 0.35 | 1.11 | 0.105 | 0.67 | 0.31 | 1.48 | 0.327 |
TS-TR – 3R/3R | 0.80 | 0.46 | 1.41 | 0.439 | 1.11 | 0.54 | 2.28 | 0.767 |
Combined genotype groups* | ||||||||
Group 1 | 1 (reference) | 1 (reference) | ||||||
Group 2 | 4.20 | 1.52 | 11.56 | 0.006 | 4.54 | 1.09 | 18.92 | 0.038 |
Group 3 | 6.61 | 1.93 | 22.59 | 0.003 | 10.12 | 2.04 | 50.19 | 0.005 |
Multivariate analysis* - DFS | Multivariate analysis*– OS | |||||||
---|---|---|---|---|---|---|---|---|
Variable | HR | 95% CI |
p
| HR | 95% CI |
p
| ||
GSTT1 (nullvs. Present) | 1.67 | 0.96 | 2.91 | 0.071 | 2.82 | 1.41 | 5.64 | 0.003 |
RFC1 – AA | 1 (reference) | 1 (reference) | ||||||
RFC1 – GA | 2.15 | 1.00 | 4.65 | 0.051 | 1.53 | 0.57 | 4.14 | 0.402 |
RFC1 – GG | 2.64 | 1.18 | 5.90 | 0.018 | 2.62 | 0.94 | 7.31 | 0.066 |
Combined genotype groups** | ||||||||
Group 1 | 1 (reference) | 1 (reference) | ||||||
Group 2 | 3.93 | 1.42 | 10.86 | 0.008 | 3.87 | 0.92 | 16.20 | 0.064 |
Group 3 | 6.35 | 1.82 | 22.17 | 0.004 | 11.53 | 2.26 | 58.71 | 0.003 |