Table 3.
Selected co-alterations based on statistical significance.
| Pathway | Gene/ protein | All subtypes | HR+ HER2+ | HR- HER2+ | HR+HER2- | TNBC | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| (%) | (%) | (%) | (%) | (%) | |||||||
| MT | WT | MT | WT | MT | WT | MT | WT | MT | WT | ||
| Homologous recombination | BRCA1 | 3.0 | 2.7 | 1.0 | 0.6 | 0.0 | 0.8 | 0.8* | 1.8* | 6.1 | 6.0 |
| BRCA2 | 4.1 | 5.4 | 1.0 | 2.5 | 3.6 | 2.3 | 4.1* | 7.9* | 4.4 | 3.0 | |
| PALB2 | 0.7* | 1.3* | 0.0 | 0.0 | 0.0 | 0.0 | 0.5* | 2.5* | 0.9 | 0.3 | |
| DNA Damage Sensors | ATM | 1.6 | 2.3 | 2.0 | 3.1 | 1.2 | 1.5 | 1.9 | 2.9 | 1.2 | 1.2 |
| ATRX | 1.0 | 0.6 | 0.0 | 0.0 | 2.3 | 1.4 | 1.2 | 0.5 | 0.7 | 0.6 | |
| CHEK2 | 2.0 | 1.5 | 3.6 | 1.4 | 1.3 | 1.6 | 2.9 | 2.1 | 1.0 | 0.3 | |
| Possible predictors of CPI benefit | PD-1 | 49.8 | 50.0 | 38.5 | 52.2 | 66.7 | 66.7 | 37.5 | 41.7 | 66.0 | 58.1 |
| PD-L1 TC (SP142) | 6.9* | 4.2* | 3.3 | 0.7 | 8.1 | 4.9 | 3.3 | 3.0 | 11.6 | 8.1 | |
| PD-L1 IC (SP142) | 29.2 | 26.6 | 50.0 | 18.8 | 25.0 | 27.3 | 12.9 | 16.7 | 42.1 | 40.4 | |
| MSI | 0.7 | 0.6 | 0.0 | 0.0 | 1.2 | 0.8 | 0.8 | 0.4 | 0.7 | 1.2 | |
| TMB-High (≥10/Mb) | 22.9* | 18.8* | 36.0* | 17.2* | 29.8 | 25.9 | 21.2* | 16.6* | 23.6 | 21.3 | |
| Chromatin remodeling | ARID1A | 12.4* | 18.6* | 19.4 | 23.8 | 7.1 | 18.9 | 17.1 | 21.5 | 5.8 | 9.6 |
| ARID2 | 0.7 | 0.8 | 0.0 | 1.9 | 0.0 | 0.7 | 0.8 | 0.6 | 0.6 | 0.9 | |
| RAS-RAF-MEK-ERK | HRAS | 0.7* | 0.1* | 0.0 | 0.0 | 0.0 | 0.0 | 0.2 | 0.1 | 1.4 | 0.3 |
| KRAS | 2.0* | 1.1* | 1.0 | 0.0 | 0.0 | 0.0 | 1.9 | 1.2 | 2.2 | 2.0 | |
| NRAS | 0.2 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.2 | 0.0 | 0.3 | 0.0 | |
| BRAF | 0.5 | 0.1 | 1.0 | 0.0 | 1.2 | 0.0 | 0.6 | 0.3 | 0.4 | 0.0 | |
| Others | TP53 | 60.9* | 53.1* | 66.3 | 60.8 | 85.5 | 86.7 | 38.4* | 25.6* | 84.7 | 86.4 |
| CDH1 | 10.3* | 6.1* | 9.1* | 2.5* | 4.8 | 2.2 | 15.1* | 9.6* | 4.9* | 2.3* | |
| NF1 | 6.2* | 2.1* | 9.5* | 0.8* | 2.7 | 3.6 | 5.8* | 1.8* | 6.7* | 2.8* | |
| RB1 | 5.5* | 2.6* | 2.2 | 1.3 | 3.6 | 3.0 | 3.9* | 1.7* | 7.8 | 5.0 | |
| ERBB2 | 2.3* | 3.4* | 3.0 | 3.1 | 3.5 | 6.7 | 3.2 | 3.5 | 1.0* | 2.3* | |
MT = at least 1 pathogenic mutation in PIK3CA, AKT1, or PTEN or PTEN loss by IHC; WT = no pathogenic mutations in PIK3CA, AKT1, and PTEN; TMB = tumor mutational burden; TC, tumor cells; IC, immune cells; CPI, immune checkpoint inhibitors.
*
Statistically significant difference between MT and WT.