Table 1.
Studies of interest presenting tumoral circulating proteins in plasma and serum of patients with breast cancer
| Protein | Function | Studied population | Number of patients | Clinical association with elevated blood levels | Refs |
|---|---|---|---|---|---|
| VEGF | Angiogenesis factor | BC | 44 | Poor disease progression and late clinical stages | [96] |
| Metastatic BC | 253 | Poor clinical outcome and poor overall survival | [75] | ||
| TNBC | 21 | At baseline, associated with a good overall survival (10.2 months vs 4.2 months in the low levels group) | [99] | ||
| TNBC, non-TNBC and healthy participants |
43 (TNBC) 53 (non-TNBC) 20 (healthy participants) |
Worse response to NAC, metastasis and a poorer OS (median OS around 22 months) | [63] | ||
| TNBC | 303 | Unfavourable outcome (3-year DFS of 53% vs 85% with low serum VEGF levels) | [100] | ||
| TGF β | Cytokine controlling proliferation | BC and healthy particpants | 44 | Advanced stages | [61] |
| BC | 60 | Advanced stages | [62] | ||
| TNBC | 43 | High incidence of metastasis, relapse, and poor response to NAC | [63] | ||
| TNBC | 48 | TGF-β-related proteins were associated with TNBC tumour progression and poor outcomes | [64] | ||
| oesophageal adenocarcinoma | NA | TGF-β serum levels in metastatic patients were significantly higher compared to patients with non-metastatic disease | [65] | ||
| MMP9 | Endopeptidase involved in the degradation of extracellular matrix | BC and benign breast disease |
77 (BC) 10 (benign) |
Higher in the breast cancer group compared to the benign tumour group | [91] |
| Metastatic BC and BC |
88 (M +) 160 (M0) |
Prognostic factor | [72] | ||
| TNBC | 303 | High levels correlated with a decrease in pCR rate and a poor response to NAC | [93] | ||
| HER2 | Involved in the regulation of cell proliferation | BC | 118 | Elevated preoperative correlated with a worse prognosis | [69] |
| HER2 + M + BC | 537 | Short PFS | [70] | ||
| BC | 64 | Poor outcomes | [71] | ||
| Metastatic BC and BC |
88 (M +) 160 (M0) |
Appearance of brain metastasis | [72] | ||
| TIMP-1 | Matrix metalloproteinases inhibitor | Metastatic BC | 253 | Poor PFS and OS | [74] |
| BC | 60 | Elevated serum levels associated with lower progression-free and OS rates | [76] | ||
| HER2 + M + BC | 472 | TIMP-1 levels described as prognostic factor of shorter PFS | [70] | ||
| TIE1/2 and Ang-2 | Promotes angiogenesis | BC and healthy participants |
143 (BC) 100 (healthy patients) |
Ang-2 was higher in BC than in the healthy group and was associated with a worse OS and metastasis | [106] |
| BC and benign breast disease |
127 (BC) 38 (benign breast disease) |
Ang-2 was higher in BC than in the benign breast disease group | [107] | ||
| M + BC | 181 | High Ang-2 levels at baseline associated with poor PFS. Both Ang-2 and serum Tie2 appeared as prognostic factors of poor OS | [108] | ||
| M + BC | 58 | Good prognostic value, short median OS (around 20 months) and short median PFS | [109] | ||
| HP | Captures haemoglobin during haemolysis and inhibits oxidative activity | BC | 6606 | Poor clinical outcomes | [113] |
| TNBC and healthy participants |
41 (TNBC) 10 (healthy patients) |
Poor prognosis and low survival rate | [114] | ||
| TNBC and non-TNBC |
30 (TNBC) 30 (non-TNBC) |
High expression in TNBC group compared to non-TNBC group | [115] | ||
| CA15-3 and CEA | Prognostic markers for BC | TNBC | 247 | Elevated CEA and CA15-3 levels associated with short OS and DFS rates | [118] |
| TNBC | 604 | High risk of death | [119] | ||
| VE-cadherin | Plays a crucial role in endothelial adherens junction assembly and maintenance | BC | 48 | Predictive factor for recurrence | [83] |
| Hormone-resistant M + BC | 141 | Prognostic factor for both PFS and OS | [84] | ||
| HGF | Involved in morphogenesis, cell and tissue survival, and cellular growth | BC | 134 | Appearance of metastases | [78] |
| BC | 34 | Poor prognosis and a high risk of progression | [79] | ||
| BC | 121 | Metastasis | [80] | ||
| IGF-I and PDGF | Regulator of growth, survival, migration and invasion | TNBC, non-TNBC and healthy participants |
43 (TNBC) 53 (non-TNBC) 20 (healthy participants) |
Metastasis and recurrence | [63] |
| BC | 110 | Associated with high serum PDGF levels, IGF-I may increase this risk of recurrence | [110] | ||
| LRP6N | Co-receptor for Wnt signal induction | BC | 295 | Diagnostic marker for the early detection of breast cancer metastasis | [77] |
| PD1/PDL1 | Immune checkpoints | TNBC | 66 | Predictive factors of treatment response | [132] |
| HER2 + M + BC | 387 | High serum PDL1 level before treatment strongly linked to longer OS in the lapatinib group compared to the trastuzumab group | [133] | ||
| M + BC | 208 | Short PFS of metastatic breast cancer and a poor prognosis | [134] |
Ang2: Angiopoietin 2, ApoC-I: Apolipoprotein I-C, BC: Breast cancer, CA15-3: Cancer antigen 15–3, CEA: Carcinoembryonic antigen, ELISA: Enzyme-linked immunosorbent assay, HER2: Human epidermal growth factor receptor 2, HGF: Hepatocyte growth factor, HP: Haptoglobin, IGF: Insulin-like growth factor, LRP6N: LRP6 ectodomain, MMP9: Matrix metalloproteinase 9, M + : metastatic, NAC: Neoadjuvant chemotherapy, OS: Overall survival, pCR: pathological complete response, PDGF: Platelet-derived growth factor, PD1: Programmed cell death protein 1, PDL1: Programme death ligand 1, PFS: Progression free survival, TGF β: Transforming growth factor β, Tie-1/2: Tyrosine kinase with immunoglobulin and epidermal growth factor-homology domains ½, TIMP-1: Tissue inhibitor of metalloproteinase 1, TNBC: Triple negative breast cancer, VEGF: Vascular endothelial growth factor