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Targeting insulin-like growth factor-1 (IGF-1) by using metformin in non-diabetic metastatic breast cancer female
Hager Salah1,2, Hoda Rabea3, Mostafa S Sheemy4
1Clinical pharmacy department, King Hamad University Hospital- Royal Medical Services, Muharraq Governorate, Bahrain.
Purpose:
Insulin-like growth factor-1 (IGF-1) may play a role in breast cancer (BC) development. Metformin was found to exert anti-cancer function in several studies, partly by interference with the IGF-1 signaling pathway and reducing its blood levels. Therefore, our study aimed primarily to find out how metformin affected both IGF-1 levels and clinical outcomes in metastatic breast cancer patients (MBC) and secondarily to identify the correlation between post-treatment IGF-1 decline rates and BC prognosis and metastasis.
Methods:
Fifty MBC female patients were randomly assigned to either the control group (who were administered conventional chemotherapy) and the intervention group (treated with metformin plus chemotherapy). An enzyme-linked immunosorbent assay (ELISA) was used to detect IGF-1 levels at baseline and three months post-treatment.
Results:
IGF-1 levels in the metformin group were significantly lower than in the control group (p = 0.011). Furthermore, the percentage of post-treatment drop in IGF-1 levels differed significantly between the control and metformin groups (p = 0.001). Patients whose IGF-1 levels increased after treatment had a statistically significant occurrence of progressive disease (disease progression) in the control group higher than in the metformin group (92.9% versus 87.5%).
Conclusion:
The co-administration of metformin with chemotherapy significantly inhibited the IGF-1 signaling pathway, which reduced progressive diseases and reduced mortality in non-diabetic MBC patients. However, while metformin exerts a robust IGF-1 lowering effect, combination chemotherapy and low metastasis burden may further enhance this effect.
Trail Registration:
Our trial was registered at clinicaltrials.gov (ID no. NCT04143282).
Insights
Metformin combined with chemotherapy significantly lowered insulin-like growth factor-1 (IGF-1) levels in metastatic breast cancer patients. This reduction correlated with decreased disease progression, suggesting metformin
Area of Science:
- Oncology
- Endocrinology
- Pharmacology
Background:
- Insulin-like growth factor-1 (IGF-1) signaling is implicated in breast cancer (BC) development.
- Metformin demonstrates anti-cancer properties, potentially by modulating the IGF-1 pathway.
- This study investigates metformin's impact on IGF-1 and clinical outcomes in metastatic breast cancer (MBC).
Purpose of the Study:
- To evaluate the effect of metformin on IGF-1 levels and clinical outcomes in MBC patients.
- To correlate post-treatment IGF-1 decline rates with BC prognosis and metastasis.
- To assess metformin's role in the IGF-1 signaling pathway in MBC.
Main Methods:
- A randomized controlled trial involving 50 MBC patients.
- Intervention group received metformin plus chemotherapy; control group received chemotherapy alone.
- Insulin-like growth factor-1 (IGF-1) levels were measured at baseline and three months post-treatment using ELISA.
Main Results:
- Metformin significantly reduced IGF-1 levels compared to the control group (p=0.011).
- A significantly greater post-treatment drop in IGF-1 was observed in the metformin group (p=0.001).
- Patients with increased IGF-1 post-treatment showed higher rates of progressive disease, particularly in the control group (92.9% vs. 87.5% in metformin group).
Conclusions:
- Co-administration of metformin with chemotherapy inhibits the IGF-1 signaling pathway in non-diabetic MBC patients.
- This inhibition is associated with reduced disease progression and mortality.
- Combination chemotherapy and a low metastasis burden may enhance metformin's IGF-1 lowering effect.
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