The insulin-like growth factor family and breast cancer prognosis: A prospective cohort study among postmenopausal women in Denmark

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Loa Kalledsøe, Lars Ove Dragsted, Louise Hansen, Cecilie Kyrø, Henning Grønbæk, Anne Tjønneland, Anja Olsen

Objective: Circulating levels of insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) have been associated with breast cancer (BC) risk. The evidence in relation to BC prognosis is limited. We aimed to evaluate the association between pre-diagnostic serum levels of IGF-I, IGF-II, IGFBP-2, IGFBP-3 and BC prognosis (i.e. recurrence, BC specific mortality and all-cause mortality) among women diagnosed with BC. We hypothesized that higher serum levels of IGFs and IGFBPs were associated with poor BC prognosis and that the associations were modified by estrogen receptor (ER) status.

Design: From the Danish Diet, Cancer and Health cohort, 412 postmenopausal women diagnosed with incident BC within 5 years of cohort baseline (1993-1997) were identified. Baseline serum samples were analyzed for IGF-I, IGF-II, IGFBP-2 and IGFBP-3. Follow-up was carried out through 2014 by linkage to national Danish registries. Exposures were related to BC prognosis by Cox Proportional Hazard models; effect modification by ER status was investigated and sensitivity analyses by follow-up time were made.

Results: During a median of 15 years, 106 women experienced recurrence and 172 died (118 due to BC). Overall, no associations were observed between IGF-I, IGF-II, IGFBP-2, IGFBP-3 and BC prognosis and no effect modification by ER status was observed. However, higher levels of IGF-II were associated with higher BC specific mortality [Hazard Ratio (HR) (95% Confidence Intervals (CI)): 1.43 (1.01-2.04)] within 10 years of follow-up. Likewise, higher levels of IGFBP-2 were associated with higher BC specific mortality [HR (95% CI): 1.87 (1.19-2.94)] within 5 years of follow-up. In contrast, higher levels of IGFBP-3 were associated with lower risk of recurrence [HR (95% CI): 0.76 (0.60-0.97)] at 5 years of follow-up and BC specific mortality [HR (95% CI): 0.80 (0.65-0.98)] within 10 years of follow-up.

Conclusions: The present study did not support an association between higher serum levels of IGFs, IGFBPs and adverse BC prognosis. However, it is possible that the role of the IGF family in the etiology of the 5-10 year BC prognosis is different from that of longer-term BC prognosis.

Original languageEnglish
JournalGrowth Hormone & I G F Research
Volume44
Pages (from-to)33-42
Number of pages10
ISSN1096-6374
DOIs
Publication statusPublished - 2019

    Research areas

  • The Faculty of Science - Prospective, Breast cancer prognosis, Hormones, Insulin like growth factor family, Postmenopausal women

ID: 211853526