Table 4.
Clinical studies assessing predictive biomarkers in relation to the activity or efficacy of platinum in TNBC.
| Study | Study design | Setting | Markers | Positively associated with clinical endpoints |
|---|---|---|---|---|
| Silver(2010)5 | Phase I/II | Neoadjuvant | Age,BRCA1 mutation status,BRCA1 mRNA Expression,BRCA1 Promoter Methylation,ΔNp63/TAp73,p53 Mutation, Array Mining | Young age, low BRCA1 mRNA expression, BRCA1 promoter methylation, p53 nonsense or frameshift mutations, and a gene expression signature of E2F3 activation |
| Vollebergh(2011)38 | Prospective | Adjuvant | BRCA1-likeCGH classifier | BRCA1-likeCGH profile |
| Birkbak(2012)41 | Retrospective | Neoadjuvant | NtAI | Higher levels of NtAI |
| Vollebergh(2014)39 | Retrospective | Adjuvant | BRCA-likeCGH classifier | BRCA-likeCGH profile |
| Richardson(2014)45 | Retrospective | Neoadjuvant | BRCA1 mutation status, HRD score | BRCA1 mutation and HRD score ≥ 42 |
| Telli(2015)67 | Phase II | Neoadjuvant | BRCA1 mutation status, HRD-LOH | BRCA1 mutation and higher HRD-LOH score |
| Isakoff(2015)10 | Phase II | First/second-line | BRCA1/2 mutation status,HRD-LOH/HRD-LST score,p63/p73,PAM50 gene expression subtypes,p53 and PIK3CA mutation status | BRCA1 mutation and higher HRD-LOH/HRD-LST score |
| Kaklamani(2015)47 | Phase II | Neoadjuvant | HRD score, BRCA1/2 mutation status, protein-based biomarkers (Ki67, TP53, androgen receptor, Cyclin E, CDK2, Cyclin D, CDK4, Pin1 and Smad3) | HRD score ≥ 42, BRCA1/2 mutation and cytoplasmic CDK2 |
| Telli(2015)46 | Phase II | Neoadjuvant | HRD score, BRCA1/2 mutation status | HRD score ≥ 42 and BRCA1/2 mutation |
| GeparSixto/Von Minckwitz (2015)66 and Denkert(2015)61 | Phase II | Neoadjuvant | HRD score, Stromal TILs, mRNA expression of immunoactivating factors (CXCL9, CCL5, CD8A, CD80, CXCL13, IGKC, CD21), immunosuppressive factors (IDO1, PD-1, PD-L1, CTLA4, FOXP3) | HRD score ≥ 42, Increased levels of stromal TILs and all 12 immune mRNA markers |
| Tutt(2015)69 | Phase III | First line | BRCA1/2 mutation status,HRD score | BRCA1/2 mutation |
| Sharma(2015)57 | Prospective | Neoadjuvant | Hematological toxicity | Thrombocytopenia |
ORR: overall response rate. PFS: progression-free survival. OS: overall survival. pCR: pathologic complete response. CGH: comparative genomic hybridization. NtAI: allelic imbalance extending to the telomere. HRD: homologous recombination deficiency. LDH: loss of heterozygosity. LST: large-scale state transitions. RR: response rate.