Table 1.
Molecular Biomarkers in Inflammatory Breast Cancer
| Biomarker | Biomarker´s Characteristics | Prognostic Significance | Therapeutics Options | References |
|---|---|---|---|---|
| Tumor-associated biomarkers | ||||
| Hormone receptors | ER-/PR- | [2,16–18] | ||
| HER2 | HER2+ | antiHER2 | [2,16–18] | |
| E-cadherin | Intracellular translocation | Cancer cells migration | [7] | |
| IBC-related genetic biomarkers | ||||
| MYC | MYC amplif. in TN IBC | [19] | ||
| p53 | Mutation, cytoplasmic sequestration | ↑ risk of death | [21,22] | |
| ERBB2 | ERBB2 mutation | Potential target for HR+ IBC | [20] | |
| miRNAs | ||||
| miR-301b, miR-451, miR-15a, miR-342-3p, miR-342-5p | Potential diagnostic biomarkers | [23] | ||
| miR-19a, miR-7, miR-324-5p | Better prognosis | [23] | ||
| miR-21, miR-205 | Poorer prognosis | [23] | ||
| miR-26b and miR-205 | Lower expression | Shorter MFS and OS | [24,25] | |
| WISP3 | Loss of WISP3 | ↑ invasive potential, tumor cells growth | [26] | |
| Rhoc GTPase | Overexpress. | ↑ angiogenesis, invasiveness, tumor cells motility | [27–29] | |
| MARCKS | Overexpress. | ↓ MFS | [32,33] | |
| Caveolin 1 | Upregulation | ↑ invasiveness | [30,31] | |
| VEGF-D | Upregulation | ↑ angiogenic and angioinvasive potential | Angiogenesis inhibitors (Bevacizumab) | [36–40] |
| PDGFRα | Upregulation | ↑ angiogenesis | PDGFRα inhibitor (BLU-285), monoclonal antibodies (olaratumab) | [7] |
| EGFR | EGFR+ | Chemotherapy resistance, ↑ recurrence rates, ↑ risk of death | [7,41] | |
| Cyclin E | Overexpress. | Tumors cells invasion and chemoresistance | CDK inhibitors – targeting cyclin E/CDK2 complex (dinaciclib) | [42–45] |
| EZH2 | Expression | Higher risk of radioresistance | Radiosensitizers (CDK inhibitors) | [46] |
| Affected pathways | ||||
| NF-κB pathway | Upregulation of antiapoptotic factors | Resistance to chemotherapy | [47–49] | |
| JAK/STAT pathway | pJAK2 and pSTAT3 activation | Survival of cancer cells, chemotherapy resistance | [50–53] | |
| HER/PI3K/mTOR pathway | mTOR activation through pS6 | Oncogenic signaling promotion | mTOR inhibitor (everolimus) | [50,56,57] |
| COX2 pathway | overexpress. | chronic inflammation, poorer OS | [58,59] | |
| Tumor microenvironment associated biomarkers | ||||
| CD44, CD49f, CD133/2 | Overexpress. in TME | Markers of stem cells – phenotype of IBC influence | [60] | |
| CD68 | Overexpress. in TME | Markers of macrophages – phenotype of IBC influence | [60] | |
| CSF1 | TAMs polarisation | Proliferation, metastasis, angiogenesis | antiCSF1 | [7] |
| IL-6 | Upregulation | Proliferation, metastasis, angiogenesis | anti Il-6 | [54,55] |
| PDL1 | Overexpress. | T-cells exhaustion | anti-PDL1 | [59,66–69,83] |
| Blood-based biomarkers | ||||
| CTC | Detectable CTC – prognostic significance | Shorter DFS and OS, lower levels of myeloid-DCs | [71,74–76] | |
| MMP2 | High baseline levels – prognostic significance | Better DFS and OS | [78] | |
| MMP9 | Low baseline levels – prognostic significance | Better DFS and OS | [78] | |