IGF-1 and risk of additional breast cancer in the WHEL study

Abstract

IGF1, IGF-binding protein-3 (IGFBP-3), IGFBP-1, insulin, leptin, and adiponectin have been inconsistently associated with breast cancer incidence. We explore how these factors are related to breast cancer recurrence and how tamoxifen treatment is related to IGF1 levels among breast cancer survivors in the Women's Healthy Eating and Living (WHEL) study. A nested case-control design was used to match breast cancer cases (who had an additional breast cancer event) to controls. Baseline blood samples from 510 matched cases and controls were analyzed for IGF1 levels; a subset of 188 pairs were analyzed for five other hormones and binding proteins. Median follow-up was 7.3 years. Matching was on recruitment site, cancer stage, age at cancer diagnosis, dates of cancer diagnosis, and randomization. Cox proportional hazards regression models, stratified on case-control pair, were used to assess the associations. Insulin, IGFBP-1, IGFBP-3, leptin, and adiponectin did not significantly predict recurrence of breast cancer. IGF1 was positively, but not significantly, associated with recurrence (hazard ratio (HR): 1.33 (95% confidence interval (CI) 0.98-1.81)) in the unadjusted analyses. Adjusting for menopausal status and tamoxifen use attenuated the HR to 1.07 (95% CI 0.76-1.40). Analyses of case-control pairs with discordant tamoxifen use show opposing HR: IGF1 predicts higher risk of recurrence if cases did not receive tamoxifen treatment. In conclusion, no significant association was found between IGF1 levels, or other related factors, and risk of additional breast cancer among breast cancer survivors. Tamoxifen can confound analysis of IGF1 and recurrence. This supports re-evaluating significance of IGF1 to breast cancer recurrence.

Associations of insulin‐like growth factor and insulin‐like growth factor binding protein‐3 with mortality in women with breast cancer

“…One study reported that the risk of recurrence in 110 postmenopausal breast cancer patients was higher in the fourth quartile (IGF‐1 > 212.5 ng ml −1 ) compared to the first (IGF‐1 < 139.2 ng ml −1 ), but this was not statistically significant22; another reported that lower levels of IGF‐1 were associated with improved survival in 130 African‐American/Hispanic breast cancer patients, although this study was based on both pre‐ and postmenopausal women 32. Results from the WHEL study reported that there was no association between IGF‐1 levels and recurrence, but WHEL enrolled patients many years after diagnosis, and survival data were not presented, so is not comparable to the present study 33. Finally, Goodwin et al found no association between IGF‐1 levels in 512 women without diabetes, and either distant recurrence or death 23.…”

Advanced Hepatic Fibrosis in Fatty Liver Disease Linked to Hyperplastic Colonic Polyp

“…Insulin binds to IGF-1 receptors and plays an important role in cell proliferation, apoptosis, and increased production of vascular endothelial growth factor, an angiogenetic factor that supports tumor growth and may play a role in the development and growth of HPs [30]. …”

Identification of the IGF1/PI3K/NF κB/ERK gene signalling networks associated with chemotherapy resistance and treatment response in high-grade serous epithelial ovarian cancer

“…Insulin-like growth factor is produced by different cell types, and its role in cancer is well documented in prostate cancer, breast cancer, colorectal cancer and melanoma, where increased risks to these cancers were associated with higher IGF1 levels [30-35]. Also, the potential role of IGF1, along with IGFBP3, as prognostic markers that can predict mortality in men with advanced prostate cancer, was reported in a recent clinical study [36].…”