Background
Methods
Patients and tumor samples
Number of patients | (%) | |
---|---|---|
204 | 100 | |
Age | ||
Median, range | 56 | 29–86 |
<55 years | 98 | 48.0 |
≥55 years | 106 | 52.0 |
T | ||
T1 | 84 | 41.2 |
T2 | 97 | 47.5 |
T3 | 10 | 4.9 |
T4 | 13 | 6.4 |
N | ||
N0 | 132 | 64.7 |
N1 | 46 | 22.5 |
N2 | 18 | 8.8 |
N3 | 8 | 3.9 |
Histology | ||
Ductal | 163 | 79.9 |
Lobular | 13 | 6.4 |
Othera
| 28 | 13.7 |
SBR-EE grade | ||
1 | 9 | 4.5 |
2 | 60 | 29.9 |
3 | 132 | 65.7 |
NE | 3 | |
Adjuvant chemotherapy | ||
No | 60 | 29.7 |
Yes | 142 | 70.3 |
Missing | 2 |
Tissue processing and DNA extraction
PIK3CA mutation detection
EGFR amplification
Detection of PTEN and other chromosome 10 sequence copy number variations (CNV) by Multiplex Ligation-dependent Probe Amplification
EGFR protein level
Statistical analysis
Results
Patients and Tumor’s characteristics
EGFR/PI3K/PTEN pathway alterations and clinicopathological correlations
Patients’ characteristics |
EGFR gene status | EGFR protein level |
PIK3CA mutations |
PTEN status | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Normal | Deletion | Amplifi-cation | Polysomy |
p
| Lower tercile | Middle tercile | Upper tercile |
p
| Exon 9 | Exon 20 | No |
p
| Deletion | No deletion |
p
| |||||||||||||
N | % | N | % | N | % | N | % | N | % | N | % | N | % | N | % | N | % | N | % | N | % | N | % | |||||
Age | 0.119 | 0.412 | 0.347 | 0.394 | ||||||||||||||||||||||||
<55 years | 76 | 49.3 | 6 | 54.5 | 11 | 61.1 | 5 | 25.0 | 31 | 48.4 | 27 | 43.5 | 35 | 55.6 | 5 | 35.7 | 6 | 35.3 | 87 | 50.3 | 23 | 53.5 | 72 | 45.9 | ||||
≥55 years | 78 | 50.7 | 5 | 45.5 | 7 | 38.9 | 15 | 75.0 | 33 | 51.6 | 35 | 56.5 | 28 | 44.4 | 9 | 64.3 | 11 | 64.7 | 86 | 49.7 | 20 | 46.5 | 85 | 54.1 | ||||
T status | 0.878 | 0.836 | 0.384 | 0.387 | ||||||||||||||||||||||||
T1 | 63 | 40.9 | 4 | 36.4 | 9 | 50.0 | 8 | 40.0 | 25 | 39.1 | 25 | 40.3 | 28 | 44.4 | 8 | 57.1 | 8 | 47.1 | 68 | 39.3 | 15 | 34.9 | 67 | 42.7 | ||||
T2+ | 91 | 59.1 | 7 | 63.6 | 9 | 50.0 | 12 | 60.0 | 39 | 60.9 | 37 | 59.7 | 35 | 55.6 | 6 | 42.9 | 9 | 52.9 | 105 | 60.7 | 28 | 65.1 | 90 | 57.3 | ||||
N status | 0.234 | 0.182 | 0.491 | 0.475 | ||||||||||||||||||||||||
N0 | 103 | 66.9 | 6 | 54.5 | 8 | 44.4 | 14 | 70.0 | 47 | 73.4 | 36 | 58.1 | 40 | 63.5 | 11 | 78.6 | 10 | 58.8 | 111 | 64.2 | 30 | 69.8 | 99 | 63.0 | ||||
N+ | 51 | 33.1 | 5 | 45.5 | 10 | 55.6 | 6 | 30.0 | 17 | 26.6 | 26 | 41.9 | 23 | 36.5 | 3 | 21.4 | 7 | 41.2 | 62 | 35.8 | 13 | 30.2 | 58 | 37.0 | ||||
SBR-EE grade | 0.466 | 0.871 | 0.038 | <0.001 | ||||||||||||||||||||||||
I-II | 49 | 32.5 | 4 | 36.4 | 6 | 33.3 | 10 | 50.0 | 22 | 34.9 | 19 | 30.7 | 21 | 34.4 | 9 | 64.3 | 7 | 41.2 | 53 | 31.2 | 4 | 9.8 | 63 | 40.4 | ||||
III | 102 | 67.5 | 7 | 63.6 | 12 | 66.7 | 10 | 50.0 | 41 | 65.1 | 43 | 69.3 | 40 | 65.6 | 5 | 35.7 | 10 | 58.8 | 117 | 68.8 | 37 | 90.2 | 93 | 59.6 | ||||
Histology | 0.102 | 0.974 | 0.103 | 0.526 | ||||||||||||||||||||||||
Ductal | 119 | 77.3 | 11 | 100 | 17 | 94.4 | 15 | 75.0 | 50 | 78.1 | 50 | 80.7 | 50 | 79.4 | 12 | 85.7 | 10 | 58.8 | 141 | 81.5 | 36 | 83.7 | 123 | 78.3 | ||||
Lobular and other | 35 | 22.7 | 0 | 0.0 | 1 | 5.6 | 5 | 5.0 | 14 | 21.2 | 12 | 19.3 | 13 | 20.6 | 2 | 14.3 | 7 | 41.8 | 32 | 18.5 | 7 | 16.3 | 34 | 21.7 | ||||
EGFR Gene Status | - | 0.164 | 0.873 | 0.224 | ||||||||||||||||||||||||
Normal | 154 | 100 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 47 | 74.6 | 51 | 82.3 | 44 | 69.8 | 11 | 78.6 | 13 | 76.4 | 130 | 75.6 | 33 | 76.8 | 120 | 76.9 | ||||
Deletion | 0 | 0.0 | 11 | 100 | 0 | 0.0 | 0 | 0.0 | 3 | 4.8 | 3 | 4.8 | 3 | 4.8 | 0 | 0.0 | 2 | 11.8 | 9 | 5.2 | 0 | 0.0 | 11 | 7.0 | ||||
Amplification | 0 | 0.0 | 0 | 0.0 | 18 | 100 | 0 | 0.0 | 4 | 6.3 | 2 | 3.2 | 11 | 17.5 | 1 | 7.1 | 1 | 5.9 | 16 | 9.3 | 5 | 11.6 | 12 | 7.8 | ||||
Polysomy | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 20 | 100 | 9 | 14.3 | 6 | 9.7 | 5 | 7.9 | 2 | 14.3 | 1 | 5.9 | 17 | 9.9 | 5 | 11.6 | 13 | 8.3 | ||||
EGFR Protein level | 0.164 | - | 0.180 | 0.110 | ||||||||||||||||||||||||
Lower tercile | 47 | 33.1 | 3 | 33.3 | 4 | 23.5 | 9 | 45.0 | 64 | 100 | 0 | 0.0 | 0 | 0.0 | 3 | 27.3 | 4 | 26.7 | 57 | 35.0 | 9 | 21.4 | 53 | 36.8 | ||||
Middle tercile | 51 | 35.9 | 3 | 33.3 | 2 | 11.8 | 6 | 30.0 | 0 | 0.0 | 62 | 100 | 0 | 0.0 | 7 | 63.6 | 4 | 26.7 | 51 | 31.3 | 14 | 33.3 | 47 | 32.6 | ||||
Upper tercile | 44 | 31.0 | 3 | 33.3 | 11 | 64.7 | 5 | 25.0 | 0 | 0.0 | 0 | 0.0 | 63 | 100 | 1 | 9.1 | 7 | 46.6 | 55 | 33.7 | 19 | 45.3 | 44 | 30.6 | ||||
PIK3CA Mutations | 0.873 | 0.180 | - | 0.565 | ||||||||||||||||||||||||
Exon 9 | 11 | 7.1 | 0 | 0.0 | 1 | 5.6 | 2 | 10.0 | 3 | 4.7 | 7 | 11.3 | 1 | 1.60 | 14 | 100 | 0 | 0.0 | 0 | 0.0 | 1 | 2.3 | 12 | 7.6 | ||||
Exon 20 | 13 | 8.4 | 2 | 18.2 | 1 | 5.6 | 1 | 5.0 | 4 | 6.2 | 4 | 6.4 | 7 | 11.1 | 0 | 0.0 | 17 | 100 | 0 | 0.0 | 3 | 7.0 | 12 | 7.6 | ||||
No | 130 | 84.5 | 9 | 81.8 | 16 | 88.8 | 17 | 85.0 | 57 | 89.1 | 51 | 82.3 | 55 | 87.3 | 0 | 0.0 | 0 | 0.0 | 173 | 100 | 39 | 90.7 | 133 | 84.8 | ||||
PTEN Status | 0.224 | 0.110 | 0.565 | - | ||||||||||||||||||||||||
Deletion | 33 | 21.6 | 0 | 0.0 | 5 | 29.4 | 5 | 27.8 | 9 | 14.5 | 14 | 23.0 | 19 | 30.2 | 1 | 7.7 | 3 | 20.0 | 39 | 22.7 | 43 | 100 | 0 | 0.0 | ||||
No deletion | 120 | 78.4 | 11 | 100 | 12 | 70.6 | 13 | 72.2 | 53 | 85.5 | 47 | 77.0 | 44 | 69.8 | 12 | 92.3 | 12 | 80.0 | 133 | 77.3 | 0 | 0.0 | 157 | 100 |
Survival analyses
N | RFS | OS | |||||
---|---|---|---|---|---|---|---|
Events | 5-y RFS | HR (95 % CI) | Events | 5-y OS | HR (95 % CI) | ||
Age | |||||||
<55 years | 98 | 21 | 79.9 | 1 | 17 | 84.1 | 1 |
≥55 years | 106 | 31 | 72.6 | 1.29 [0.74; 2.24] | 30 | 78.9 | 1.51 [0.83; 2.73] |
p = 0.370 |
p = 0.174 | ||||||
T | |||||||
T1 | 84 | 11 | 88.3 | 1 | 11 | 90.7 | 1 |
T2+ | 120 | 41 | 67.5 | 2.91 [1.50; 5.67] | 36 | 74.7 | 2.48 [1.26; 4.88] |
p = 0.001 |
p = 0.006 | ||||||
N | |||||||
N- | 132 | 20 | 86.9 | 1 | 21 | 89.0 | 1 |
N+ | 72 | 32 | 56.1 | 3.56 [2.03; 6.22] | 26 | 66.8 | 2.58 [1.45; 4.59] |
p < 0.001 |
p = 0.001 | ||||||
SBR-EE grade | |||||||
1-2 | 69 | 17 | 79.9 | 1 | 15 | 86.3 | 1 |
3 | 132 | 35 | 73.7 | 1.13 [0.63; 2.02] | 32 | 78.4 | 1.21 [0.65; 2.24] |
p = 0.676 |
p = 0.541 | ||||||
Histology | |||||||
Ductal | 163 | 42 | 75.4 | 1 | 40 | 80.0 | 1 |
Lobular/Other | 41 | 10 | 78.7 | 0.93 [0.47; 1.86] | 7 | 86.6 | 0.67 [0.30; 1.49] |
p = 0.848 |
p = 0.325 | ||||||
Adjuvant CT | |||||||
No | 60 | 21 | 66.7 | 1 | 24 | 69.1 | 1 |
Yes | 142 | 31 | 80.1 | 0.60 [0.35; 1.05] | 23 | 86.8 | 0.40 [0.23; 0.71] |
p = 0.070 |
p = 0.001 | ||||||
EGFR status | |||||||
Normal/Deletion | 165 | 41 | 78.0 | 1 | 35 | 81.8 | 1 |
Ampl./Polysomy | 38 | 11 | 65.9 | 1.36 [0.69; 2.65] | 12 | 78.5 | 1.80 [0.93; 3.49] |
p = 0.368 |
p = 0.075 | ||||||
PIK3CA status | |||||||
No mutation | 173 | 40 | 78.0 | 1 | 36 | 83.2 | 1 |
Exon 9 | 14 | 7 | 61.5 | 2.62 [1.17; 5.86] | 7 | 69.2 | 2.55 [1.13; 5.74] |
Exon 20 | 17 | 5 | 67.8 | 1.38 [0.54; 3.50] | 4 | 70.5 | 1.23 [0.44; 3.46] |
p = 0.048 |
p = 0.063 | ||||||
EGFR protein level | |||||||
Lower and middle tercile | 126 | 30 | 79.4 | 1 | 27 | 84.1 | 1 |
Upper tercile | 63 | 20 | 66.0 | 1.54 [0.87; 2.72] | 17 | 73.8 | 1.42 [0.78; 2.62] |
p = 0.131 |
p = 0.247 | ||||||
PTEN status | |||||||
No deletion | 157 | 38 | 78.5 | 1 | 33 | 83.4 | 1 |
Deletion | 43 | 13 | 67.7 | 1.38 [0.74; 2.60] | 13 | 75.1 | 1.66 [0.87; 3.16] |
p = 0.309 |
p = 0.117 |
HR | 95 % CI |
p
| |
---|---|---|---|
T | 0.008 | ||
T1 | 1 | ||
T2+ | 2.48 | [1.21; 5.07] | |
N | <0.001 | ||
N- | 1 | ||
N+ | 4.17 | [2.23; 7.78] | |
Adjuvant CT | 0.003 | ||
No | 1 | ||
Yes | 0.39 | [0.22; 0.70] | |
PIK3CA Exon 9 Mutation | 0.001 | ||
No | 1 | ||
Yes | 6.38 | [2.42; 16.8] | |
EGFR protein level | 0.011 | ||
Lower and middle tercile | 1 | ||
Upper tercile | 2.22 | [1.22; 4.03] |