Insulin‐like growth factor I and risk of breast cancer by age and hormone receptor status—A prospective study within the EPIC cohort

Abstract

Experimental evidence shows cross‐talk in mammary cells between estrogen, insulin‐like growth factor I (IGF‐I) and their respective receptors and possible synergistic effects of estrogen receptor (ER) activation and increased IGF‐I signaling with regard to breast tumor development, and epidemiological evidence suggests that circulating IGF‐I levels may be related more to the risk of ER‐positive than ER‐negative breast cancer. Using a case–control study nested within the prospective European EPIC cohort (938 breast cancer cases and 1,394 matched control subjects), we analyzed the relationships of prediagnostic serum IGF‐I levels with the risk of estrogen and progesterone receptor‐positive and ‐negative breast tumors. IGF‐I levels were positively associated with the risk of ER+ breast tumors overall (pre‐ and postmenopausal women combined, odds ratio (OR)Q4‐Q1 = 1.41 [95% confidence interval (CI) 1.01–1.98] for the highest vs. lowest quartile; OR = 1.17 [95% CI 1.04–1.33] per 1‐standard deviation (SD) increase in IGF‐I, ptrend = 0.01) and among women who were diagnosed with breast cancer at 50 years or older (ORQ3‐Q1 = 1.38 [95% CI 1.01–1.89]; OR = 1.19 [95% CI 1.04–1.36] per 1‐SD increase in IGF‐I, ptrend = 0.01) but not with receptor‐positive disease diagnosed at an earlier age. No statistically significant associations were observed for ER− breast tumors overall and by age at diagnosis. Tests for heterogeneity by receptor status of the tumor were not statistically significant, except for women diagnosed with breast cancer at 50 years or older (phet = 0.03 for ER+/PR+ vs. ER−/PR− disease). Our data add to a global body of evidence indicating that higher circulating IGF‐I levels may increase risk specifically of receptor‐positive, but not receptor‐negative, breast cancer diagnosed at 50 years or older.

Insulin-like growth factor-1, growth hormone, and daily cycling estrogen are associated with mammographic density in premenopausal women

“…Interestingly, a crosstalk between IGF-1 and estrogen in breast cancer development has been hypothesized [15][16][17][18]. Recently, GH action was studied in a panel of estrogen receptor-positive breast cancer cell lines, and GH significantly enhanced 17β-estradiolstimulated proliferation in these cells.…”

“…Recently, endogenous sex hormone levels and percent mammographic density were associated with breast cancer risk, both independently and in combination [14]. Interestingly, it has been hypothesized that a crosstalk operates between estrogen and the GH-IGF-1 signalling pathways in cells [15][16][17][18].…”

Circulating concentrations of insulin like growth factor-1 in female dogs with spontane-ous mammary tumours

“…In human medicine many authors (2, 15) have also found significantly higher levels of serum IGF-1 in women with breast cancer compared to healthy controls. Moreover, numerous studies have demonstrated a relationship between increased circulating levels of IGF-1 and breast cancer risk in women (9). These findings indicate that circulating IGF-1 plays an important role in mammary gland tumorigenesis both in women and female dogs.…”

“…In humans the role of IGF-1 in tumorigenesis has been investigated intensively. Some of these studies have demonstrated that an elevated serum IGF-1 concentration was associated with an increased risk of breast cancer and other cancers in humans (9). Several authors have reported increased serum IGF-1 concentrations in breast cancer patients compared with healthy control (2,15).…”

Metformina: más allá del control glucémico

“…Las hipótesis plantean un efecto secundario del hiperinsulinismo y la resistencia a la insulina, dado por la actividad mitogénica directa de esta, así como, por el aumento del Factor de Crecimiento Similar a la Insulina-tipo 1 y tipo 2 al aumentar la expresión del receptor de hormona de crecimiento en células malignas de tejido hepático, mamario, próstata y líneas celulares hemáticas 102,103 , a su vez, como marcador del potencial invasivo y antiapoptótico. Además, la hiperglucemia, si bien, bajo la "hipótesis de Warburg" 104 , es el principal sustrato metabólico para la generación de energía en las células cancerígenas 105,106 .…”