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.

中文翻译：

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胰岛素样生长因子家族与乳腺癌的预后：丹麦绝经后妇女的前瞻性队列研究。

目的

胰岛素样生长因子（IGFs）及其结合蛋白（IGFBPs）的循环水平与乳腺癌（BC）风险有关。有关BC预后的证据有限。我们旨在评估被诊断为BC的女性在诊断前血清IGF-I，IGF-II，IGFBP-2，IGFBP-3与BC预后之间的关联（即复发，BC特定死亡率和全因死亡率）。我们假设较高的血清IGFs和IGFBPs水平与不良的BC预后相关，并且该关联被雌激素受体（ER）状态所修饰。

设计

从丹麦饮食，癌症和健康研究队列中，鉴定出412名在基线基线5年（1993-1997年）内被诊断为BC的绝经后妇女。分析基线血清样品的IGF-I，IGF-II，IGFBP-2和IGFBP-3。通过与丹麦国家注册管理机构建立联系，在2014年进行了后续行动。暴露与Cox比例风险模型的BC预后相关。研究了由ER状态引起的效应改变，并根据随访时间进行了敏感性分析。

结果

在15年中位数中，有106名妇女复发，有172人死亡（118名因卑诗省）。总体而言，未观察到IGF-I，IGF-II，IGFBP-2，IGFBP-3和BC预后之间的关联，也未观察到ER状态对疗效的影响。但是，在随访10年内，较高的IGF-II水平与较高的BC特定死亡率[危险比（HR）（95％可信区间（CI））：1.43（1.01-2.04）]相关。同样，在随访的5年内，较高的IGFBP-2水平与较高的BC特定死亡率[HR（95％CI）：1.87（1.19–2.94）]相关。相比之下，在5年的随访中，较高的IGFBP-3水平与较低的复发风险[HR（95％CI）：0.76（0.60–0.97）]和BC特异性死亡率[HR（95％CI）：在随访的10年内达到0.80（0.65-0.98）。

结论

本研究不支持较高的血清IGFs，IGFBPs水平与不良BC预后之间的关联。然而，IGF家族在5-10年BC预后的病因中的作用可能与长期BC预后不同。