Table 2.
The over-review of genomic alternation in Hormone-positive breast cancer (BC)
| Gene | Alteration | Implication and comments | incidence |
|---|---|---|---|
| PIK3CA [95] | Hot spot mutation in exons 9 and 20 | PTEN loss and PIK3CA mutation were frequently concordant, suggesting different contributions to pathophysiology | 30-40% |
| ESR1 [130] | Mutation in ligand-binding domain | Hot-spot activating missense mutations (E380Q, Y537S/C/N, D538G). Treatment with AIs may exert a selective pressure favoring the expansion of ESR1-mutated clones | 18-39% |
| FGFR1 [131] | amplification | 1. 11q12-14 chromosome | Around 15-23% |
| 2. resistance to hormone therapies can be motivated by FGFR1 amplifications | |||
| 3. related to a lower PFS correlation between FGFR1 amplification and resistance to CDK4/6 inhibitors ribociclib or palbociclib | |||
| CCND1 [82,132] | amplification | 1. 11q13 chromosome BC | 9-30% |
| 2. CCND1 amplification could serve as a biomarker for the prediction of response to cyclin-dependent kinase 4/6 inhibitors | |||
| ERBB2 [133,134] | amplification | 1.Hot-spot activating missense mutations (e.g. S310F/Y, L755S, V777L); Inframe insertion exon 20 (Ex: Y772_A775dup) | In 10% ER+ BC |
| 2. HR and ERBB2 cross-talk as a mechanism for resistance to endocrine therapy | |||
| PTEN [135] | loss or mutation | Homozygous deletions; Loss-of-function mutations: truncated mutations and known inactivating missense mutations (Ex: R130Q/G) | Mutations: 5-10% |
| acquired PTEN mutation is a resistance mechanism to PI3Kα inhibitors in ER+ PIK3CA mutant BC | Loss: 30% | ||
| MDM2 [136] | amplification | Most frequently co-occurred with MDM2 amplification were CDK4 amplification, CDKN2A/B loss, and MYC amplification | 5.7% |
| AKT1 [137,138] | E17K mutation | 1. E17K mutation activates AKT1 by recruiting it to the membrane through a PI3K-independent mechanism | In 3% of ER+ BC |
| 2. E17K-AKT1, PIK3CA, and PTEN mutations are usually mutually exclusive | |||
| BRCA1/BRCA2 [139] | mutation | Truncated mutations: insertions or deletions, splice-site, nonsense (except known truncating polymorphic variant) | 3% |
| RB1 [140] | Loss of function mutations/deletions | RB-pathway dysregulation is strongly correlated with poor response to tamoxifen therapy | 20% |
| EGFR [141] | Amplifications | Aberrant EGFR expression was associated with poor prognosis in ER+ BCs, especially the Luminal B subtype | 10% of ER+ BCs |
| ERBB2 [142] | Mutations or amplification | 1. Hot-spot activating missense mutations (e.g. S310F/Y, L755S, V777L) | 20% |
| 2. A potential signaling cross-talk between EGFR or IGF1R and ERBB2, which could influence response of ERBB2-positive BCs to inhibitors |