Insulin‐like growth‐factor‐binding protein 3 is decreased in early‐stage operable pre‐menopausal breast cancer

Abstract

Insulin-like growth factor I (IGF-I) is a potent mitogen for human breast-cancer cells in vitro. In circulation, most of IGF-I is bound to IGF-binding protein 3 (IGFBP-3). This high-affinity binding is thought to have an important limiting effect on the availability of IGF-I for biological activity. To assess the availability of IGF-I for receptor binding, we determined serum levels of IGF-I and IGFBP-3 and IGF-I/IGFBP-3 ratios. In a case-control study, 150 women aged 38 to 75 years presenting with stage-I or -II breast cancer were investigated just prior to surgery (n = 76), or to irradiation one month after surgery (n = 74). The population-based control group consisted of 441 women of the same age having no breast cancer. Women reporting diabetes mellitus or other hormonal abnormalities were excluded. Premenopausal cases showed elevated IGF-I serum concentrations, decreased IGFBP-3 levels and increased IGF-I/IGFBP-3 ratios. The IGF-I/IGFBP-3 ratio was a significant breast-cancer risk factor, also after adjustment for age, family history, height, body-mass index, body-fat distribution, and serum levels of C-peptide. The relative risk was 7.34 for the highest compared with the lowest quintile of IGF-I/IGFBP-3. The presence or absence of tumor had no influence on these results. Increased levels of available IGF-I in the circulation of pre-menopausal women may contribute to the development of breast cancer.

Insulin‐like growth factor (IGF)‐I and IGF‐binding protein 3 and the risk of premenopausal breast cancer: A meta‐analysis of literature

“…5 Previous studies have suggested that using measures such as IGF-I/IGFBP-3 ratio or IGFBP-3 adjusted OR might be more accurate than IGF-I alone in quantifying the association between IGF-I levels and premenopausal breast cancer. 7,30 Although we cannot conclude whether these alternative measures are better than absolute IGF-I level or not, we found that absolute circulating IGF-I was one of the good measures to evaluate the association between IGF-I levels and premenopausal breast cancer.…”

Glycemic index in chronic disease: a review

“…Higher levels of IGF-1 were associated with breast cancer both in pre-and post-menopausal women in one study (Peyrat et al, 1993) and only in premenopausal women in two other studies (Bruning et al, 1995;Bohlke et al, 1998) where lower levels of IGFBP-3 were also found in premenopausal cases compared to controls. No associations were observed for these variables and breast cancer in postmenopausal women in two other investigations (Bruning et al, 1995;Hankinson et al, 1997) and in one study on premenopausal women (Del Giudice et al, 1998), although in the latter the control group chosen, potentially at high risk. In a small case -control study IGF-1 and IGFBP-3 were found, respectively, directly and indirectly associated with premenopausal ductal carcinoma in situ (Bohlke et al, 1998).…”

Breast cancer: further metabolic-endocrine risk markers?

“…Published studies variously report moderate elevation in premenopausal cases (Bruning et al, 1995), marked elevation in both pre-and post-menopausal cases (Peyrat et al, 1993) and no association (Favoni et al, 1995). IGF1 is synthesized mainly in the liver under growth hormone stimulation but it is not stored locally.…”