Table 2. Univariate cox regression analysis for TP53 and PIK3CA mutation (MUT) and for p53 protein expression by IHC against disease-free survival.
| Parameter | N patients | N events | HR | 95% CI | Wald's p |
|---|---|---|---|---|---|
| ENTIRE COHORT | |||||
| TP53 mutations | |||||
| YES vs. NO | 380 vs. 1386 | 101 vs. 288 | 1.34 | 1.07–1.68 | 0.011 |
| TP53 mutation type | 0.014 | ||||
| missense vs. none | 267 vs. 1386 | 78 vs. 288 | 1.51 | 1.17–1.94 | 0.001 |
| fs-indels vs. none | 64 vs. 1386 | 13 vs. 288 | 0.99 | 0.57–1.73 | 0.97 |
| nonsense vs. none | 49 vs. 1386 | 10 vs. 288 | 0.96 | 0.51–1.8 | 0.89 |
| TP53 mutated domains | 0.03 | ||||
| DBD vs. none | 225 vs. 1386 | 63 vs. 288 | 1.42 | 1.08–1.86 | 0.012 |
| other vs. none | 155 vs. 1386 | 38 vs. 288 | 1.23 | 0.88–1.73 | 0.23 |
| PIK3CA mutations | |||||
| YES vs. NO | 458 vs. 1308 | 89 vs. 300 | 0.83 | 0.65–1.05 | 0.12 |
| PIK3CA mutated domains | 0.12 | ||||
| kinase vs. none | 265 vs. 1308 | 57 vs. 300 | 0.94 | 0.71–1.24 | 0.65 |
| helical vs. none | 193 vs. 1308 | 32 vs. 300 | 0.68 | 0.48–0.99 | 0.042 |
| TP53 or PIK3CA mutations | |||||
| YES vs. NO | 734 vs. 1032 | 159 vs. 230 | 0.97 | 0.79–1.19 | 0.78 |
| Mutation breakdown | 0.006 | ||||
| PIK3CA only vs. none | 354 vs. 1032 | 58 vs. 230 | 0.71 | 0.53–0.94 | 0.018 |
| TP53 only vs. none | 276 vs. 1032 | 70 vs. 230 | 1.17 | 0.90–1.53 | 0.25 |
| both vs. none | 104 vs. 1032 | 31 vs. 230 | 1.42 | 0.97–2.07 | 0.068 |
| p53 IHC 10% cut off | |||||
| ≥ 10% vs. <10% | 848 vs. 737 | 176 vs. 162 | 0.95 | 0.76–1.17 | 0.61 |
| LUMINAL A/B | |||||
| TP53 mutations | |||||
| YES vs. NO | 143 vs. 908 | 47 vs. 171 | 1.86 | 1.34–2.57 | < 0.001 |
| TP53 mutation type | < 0.001 | ||||
| missense vs. none | 102 vs. 908 | 34 vs. 171 | 1.90 | 1.32–2.75 | < 0.001 |
| fs-indels vs. none | 24 vs. 908 | 6 vs. 171 | 1.23 | 0.54–2.78 | 0.62 |
| nonsense vs. none | 17 vs. 908 | 7 vs. 171 | 2.71 | 1.27–5.78 | 0.010 |
| TP53 mutated domains | < 0.001 | ||||
| DBD vs. none | 93 vs. 908 | 30 vs. 171 | 1.75 | 1.18–2.58 | 0.005 |
| other vs. none | 50 vs. 908 | 17 vs. 171 | 2.09 | 1.27–3.44 | 0.004 |
| PIK3CA mutations | |||||
| YES vs. NO | 331 vs. 720 | 64 vs. 154 | 0.88 | 0.66–1.18 | 0.39 |
| PIK3CA mutated domains | 0.56 | ||||
| kinase vs. none | 185 vs. 720 | 38 vs. 154 | 0.95 | 0.66–1.35 | 0.76 |
| helical vs. none | 146 vs. 720 | 26 vs. 154 | 0.80 | 0.53–1.21 | 0.29 |
| TP53 or PIK3CA mutations | |||||
| YES vs. NO | 423 vs. 628 | 92 vs. 126 | 1.07 | 0.82–1.41 | 0.61 |
| Mutation breakdown | < 0.001 | ||||
| PIK3CA only vs. none | 280 vs. 628 | 45 vs. 126 | 0.78 | 0.55–1.08 | 0.13 |
| TP53 only vs. none | 92 vs. 628 | 28 vs. 126 | 1.58 | 1.05–2.38 | 0.030 |
| both vs. none | 51 vs. 628 | 19 vs. 126 | 1.99 | 1.23–3.23 | 0.005 |
| p53 IHC 10% cut off | |||||
| ≥ 10% vs. < 10% | 485 vs. 456 | 96 vs. 94 | 0.93 | 0.7–1.24 | 0.65 |
| TNBC | |||||
| TP53 mutations | |||||
| YES vs. NO | 85 vs. 150 | 27 vs. 32 | 1.58 | 0.94–2.63 | 0.083 |
| TP53 mutation type | 0.044 | ||||
| missense vs. none | 47 vs. 150 | 19 vs. 32 | 2.16 | 1.22–3.82 | 0.008 |
| fs-indels vs. none | 20 vs. 150 | 5 vs. 32 | 1.22 | 0.48–3.14 | 0.68 |
| nonsense vs. none | 18 vs. 150 | 3 vs. 32 | 0.71 | 0.22–2.32 | 0.57 |
| TP53 mutated domains | 0.14 | ||||
| DBD vs. none | 41 vs. 150 | 15 vs. 32 | 1.86 | 1.01–3.45 | 0.047 |
| other vs. none | 44 vs. 150 | 12 vs. 32 | 1.32 | 0.68–2.57 | 0.41 |
| PIK3CA mutations | |||||
| YES vs. NO | 33 vs. 202 | 10 vs. 49 | 1.27 | 0.64–2.51 | 0.50 |
| PIK3CA mutated domains | 0.068 | ||||
| kinase vs. none | 21 vs. 202 | 9 vs. 49 | 2.00 | 0.98–4.08 | 0.056 |
| helical vs. none | 12 vs. 202 | 1 vs. 49 | 0.29 | 0.04–2.13 | 0.22 |
| TP53 or PIK3CA mutations | |||||
| YES vs. NO | 103 vs. 132 | 31 vs. 28 | 1.47 | 0.88–2.46 | 0.14 |
| Mutation breakdown | 0.29 | ||||
| PIK3CA only vs. none | 18 vs. 132 | 4 vs. 28 | 1.01 | 0.36–2.89 | 0.98 |
| TP53 only vs. none | 70 vs. 132 | 21 vs. 28 | 1.47 | 0.84–2.6 | 0.18 |
| both vs. none | 15 vs. 132 | 6 vs. 28 | 2.10 | 0.87–5.09 | 0.10 |
| p53 IHC 10% cut off | |||||
| ≥ 10% vs. < 10% | 113 vs. 102 | 30 vs. 25 | 1.09 | 0.64–1.86 | 0.74 |
| HER2-positive, pre-trastuzumab | |||||
| TP53 mutations | |||||
| YES vs. NO | 52 vs. 149 | 19 vs. 55 | 1.01 | 0.6–1.7 | 0.97 |
| TP53 mutation type | 0.48 | ||||
| missense vs. none | 42 vs. 149 | 18 vs. 55 | 1.28 | 0.75–2.19 | 0.36 |
| fs-indels vs. none | 6 vs. 149 | 1 vs. 55 | 0.62 | 0.12–3.22 | 0.57 |
| nonsense vs. none | 4 vs. 149 | 0 vs. 55 | 0.20 | 0.01–3.72 | 0.28 |
| TP53 mutated domains | 0.46 | ||||
| DBD vs. none | 31 vs. 149 | 13 vs. 55 | 1.27 | 0.7–2.33 | 0.43 |
| other vs. none | 21 vs. 149 | 6 vs. 55 | 0.69 | 0.29–1.62 | 0.38 |
| PIK3CA mutations | |||||
| YES vs. NO | 31 vs. 170 | 12 vs. 62 | 1.03 | 0.55–1.9 | 0.94 |
| PIK3CA mutated domains | 0.96 | ||||
| kinase vs. none | 17 vs. 170 | 7 vs. 62 | 1.10 | 0.5–2.41 | 0.81 |
| helical vs. none | 14 vs. 170 | 5 vs. 62 | 0.93 | 0.38–2.33 | 0.89 |
| TP53 or PIK3CA mutations | |||||
| YES vs. NO | 72 vs. 129 | 27 vs. 47 | 1.01 | 0.63–1.62 | 0.97 |
| Mutation breakdown | <0.99 | ||||
| PIK3CA only vs. none | 20 vs. 129 | 8 vs. 47 | 1.01 | 0.48–2.13 | 0.99 |
| TP53 only vs. none | 41 vs. 129 | 15 vs. 47 | 1.00 | 0.55–1.79 | 0.99 |
| both vs. none | 11 vs. 129 | 4 vs. 47 | 1.07 | 0.38–2.95 | 0.91 |
| p53 IHC 10% cut off | |||||
| ≥ 10% vs. < 10% | 92 vs. 86 | 38 vs. 23 | 1.71 | 1.02–2.87 | 0.043 |
| HER2-positive, post-trastuzumab | |||||
| TP53 mutations | |||||
| YES vs. NO | 98 vs. 179 | 8 vs. 30 | 0.47 | 0.22–1.02 | 0.06 |
| TP53 mutation type | 0.45 | ||||
| missense vs. none | 76 vs. 179 | 7 vs. 30 | 0.56 | 0.25–1.27 | 0.16 |
| fs-indels vs. none | 13 vs. 179 | 1 vs. 30 | 0.72 | 0.13–3.87 | 0.70 |
| nonsense vs. none | 10 vs. 179 | 0 vs. 30 | 0.28 | 0.02–4.89 | 0.38 |
| TP53 mutated domains | 0.16 | ||||
| DBD vs. none | 60 vs. 179 | 5 vs. 30 | 0.47 | 0.18–1.23 | 0.12 |
| other vs. none | 38 vs. 179 | 3 vs. 30 | 0.46 | 0.14–1.5 | 0.20 |
| PIK3CA mutations | |||||
| YES vs. NO | 63 vs. 214 | 3 vs. 35 | 0.28 | 0.09–0.9 | 0.032 |
| PIK3CA mutated domains | 0.18 | ||||
| kinase vs. none | 42 vs. 214 | 3 vs. 35 | 0.47 | 0.15–1.45 | 0.19 |
| helical vs. none | 21 vs. 214 | 0 vs. 35 | 0.14 | 0.01–2.37 | 0.17 |
| TP53 or PIK3CA mutations | |||||
| YES vs. NO | 134 vs. 143 | 9 vs. 29 | 0.31 | 0.15–0.66 | 0.002 |
| Mutation breakdown | 0.026 | ||||
| PIK3CA only vs. none | 36 vs. 143 | 1 vs. 29 | 0.13 | 0.02–0.92 | 0.042 |
| TP53 only vs. none | 71 vs. 143 | 6 vs. 29 | 0.39 | 0.16–0.95 | 0.038 |
| both vs. none | 27 vs. 143 | 2 vs. 29 | 0.34 | 0.08–1.44 | 0.14 |
| p53 IHC 10% cut off | |||||
| ≥ 10% vs. < 10% | 160 vs. 92 | 12 vs. 20 | 0.31 | 0.15–0.64 | 0.002 |
Notes: TAD: transactivation domain; DBD: DNA binding domain; TETRA: oligomerization domain; IHC: Immunohistochemistry; Luminal A/B: ER/PgR positive, HER2 negative.