A total of 2,370 studies were identified through PubMed databases (n = 749), Scopus (n = 330), and Web of Science (n = 1,291). After selecting and applying the inclusion and exclusion criteria, 5 articles were included in the present systematic review, according to the flow chart detailing the process of identification, selection, eligibility, and final inclusion of the studies (Fig. 1). The description of the selected studies is shown in Table 1. (Table 1.)
Table 1
Description of the selected studies.
Author | Type of Study | Characteristic Population | Sample Size | Conclusion |
Mu et al. [25] | Cohort | Italian women | 204 cases of breast cancer | High levels of IGF-1 mRNA expression were associated with small tumors, earlier stages of the disease, low grade tumors, ER or PR positive tumors, and a better prognosis. |
Mu et al. [21] | Cohort | Italian women | 204 cases of breast cancer | High levels of IGF-1 mRNA expression were associated with the luminal A and normal-like subtype, with less aggressive tumors and a better prognosis. |
Chong et al. [26] | Cohort | English women | 132 cases of breast cancer | IGF-1 mRNA levels did not correlate with clinicopathological factors. However, increased levels of IGF-1 mRNA expression were associated with higher DFS. |
Raval and Trivedi. [7] | Cohort | Indian women | 106 cases of breast cancer | Significantly lower levels of IGF-1 mRNA expression were observed in breast tumors regardless of age, menopausal status, tumor size, lymph node status and histologic grade. There were no associations with OS and DFS. |
Christodoulou et al. [27] | Cohort | Greek women | 227 cases of breast cancer | High levels of IGF-1 mRNA expression were associated with older age and absence of bone metastases. Already decreased levels of expression were associated with histological grade III and metastases. |
Chong et al. [28] | Cohort | English women | 92 cases of breast cancer | High levels of IGF-1 mRNA expression were associated with delay in developing resistance to tamoxifen. Decreased levels of IGF-1 mRNA expression were associated with tamoxifen-resistant tumors. |
ER: estrogen receptor; PR: progesterone receptor; DFS: disease-free survival; OS: overall survival. |
The association between IGF-1 mRNA expression levels in tumor tissues of women with breast cancer and the characteristics of the disease was examined by Mu et al. [25]. A significant association was found between increased levels of IGF-1 mRNA expression and small tumors (< 2 cm), earlier stages of disease (stage 1), low grade tumors (grade 1 and 2), and tumors estrogen receptor (ER) or progesterone receptor (PR) positive. Survival analysis showed that women with high IGF-1 mRNA expression had a lower risk of disease recurrence and death compared to those with low expression.
In another study, Mu et al. [21] evaluated levels of IGF-1 mRNA expression in tumor tissues of women with breast cancer. Results showed that increased levels of IGF-1 mRNA expression were associated with the luminal subtype A, normal-like, and less aggressive tumors (ER positive, low grade, node negative tumors). However, decreased levels of IGF-1 mRNA expression were associated with the basal, Human epidermal growth factor receptor 2 (HER2), and luminal B subtypes. Thus, the results of their studies showed an inverse association between IGF-1 mRNA levels and the prognosis of the disease.
Chong et al. [26] analyzed the relationship between IGF-1 mRNA expression levels in breast tumors and adjacent normal tissues (TNAs), and the clinicopathological and prognostic factors of women with breast cancer. No correlation was observed in tumor tissue and TNAs between IGF-1 mRNA expression levels and clinicopathological factors, such as histological grade, lymph node status, and tumor size. However, increased levels of IGF-1 mRNA expression in tumor tissue and TNAs were associated with increased disease free survival (DFS) while lower levels of IGF-1 mRNA were associated with shorter DFS. A similar pattern of association between IGF-1 mRNA and DFS was observed in ER-positive women. However, patients who developed local recurrence or metastasis had lower levels of IGF-1 mRNA in tumor tissue and TNAs compared to those who remained disease-free.
Raval and Trivedi [7] studied levels of IGF-1 mRNA expression in breast tumors and adjunctive normal tissues (TNAs) of women undergoing mastectomy for breast cancer treatment. Significantly lower levels of IGF-1 mRNA expression were observed in the breast tumors, regardless of age, menopausal status, tumor size, lymph node status and histological stage when compared to those in the TNAs. On the other hand, in this study, the low expression of IGF-1 mRNA was associated with stages II, III and IV breast tumors without lymphatic permeation. Thus, a significant inverse correlation was observed between stage, histological type, and levels of IGF-1 mRNA expression. Although low levels of IGF-1 mRNA expression were observed in patients who developed local recurrence/metastasis and had shorter disease free survival, significant association was not observed with respect to overall survival (OS) and DFS when breast tumors and TNAs were compared.
Christodoulou et al. [27] analyzed the in-tumor expression of IGF-1 mRNA in patients with trastuzumab-treated HER2-positive metastatic breast cancer and showed that IGF-1 mRNA expression levels were higher in patients over the age of 50 years at the time of the initial diagnosis and absence of bone metastases. In contrast, decreased levels of IGF-1 mRNA expression were associated with histological grade III, distal and mainly visceral metastases.
Chong et al. [28] evaluated the levels of IGF-1 mRNA expression in ER-positive tumors in women treated with tamoxifen. Tumors that showed high levels of IGF-1 mRNA expression were associated with a significantly longer time to develop resistance to tamoxifen. Tumors resistant to tamoxifen had significantly lower levels of IGF-1 mRNA expression when compared to tumors sensitive to tamoxifen.