Rosendahl Ann H, Björner Sofie, Ygland Rödström Maria, Jirström Karin, Borgquist Signe, Ingvar Christian, Pollak Michael N, Jernström Helena
Department of Clinical Sciences Lund, Oncology, Lund University and Skåne University Hospital, Lund, Sweden.
Department of Clinical Sciences Lund, Oncology and Therapeutic Pathology, Lund University and Skåne University Hospital, Lund, Sweden.
Front Oncol. 2021 Mar 9;11:626058. doi: 10.3389/fonc.2021.626058. eCollection 2021.
Insulin-like growth factor-I (IGF-I) and its binding proteins (BPs) have been associated with breast cancer risk, especially high IGF-I concentrations and the biologically active fraction estimated as the IGF-I/IGFBP-3 molar ratio. The relation of circulating IGF-I and IGFBP-3 concentrations with risk of breast cancer recurrence has been less documented. In addition a new member to a sub-group of the IGFBP-superfamily was recently identified, the low affinity IGFBP-7. To date, the role of systemic IGFBP-7 in breast cancer progression has not been investigated. Our purpose was to establish whether circulating IGF-I, IGFBP-3, and IGFBP-7 levels are related to recurrence-risk in breast cancer. A case-control study was nested within the population-based BCBlood cohort of 853 breast cancer patients diagnosed 2002-2010 in Sweden and followed through 2012. In total, 95 patients with recurrence and 170 controls were matched on age and tumor characteristics. Plasma IGF analytes and tumor membrane IGF-I receptor (IGF-IR) positivity were analyzed and recurrence-risk was evaluated with conditional logistic regression. Preoperative tertiles of IGF-I and IGFBP-3 were both positively associated with recurrence-risk, but not IGFBP-7. The trend was of borderline significance for IGF-I, T1:REF, T2 OR:1.6, T3 OR: 2.2 adjusted =0.057 and significant for IGFBP-3 T1:REF, T2 OR:1.2, T3 OR: 2.1 adjusted =0.042. The models were adjusted for age, anthropometric factors, smoking, and treatments. There was a significant interaction between IGFBP-7 and IGF-IR positivity on recurrence, where the highest IGFBP-7 highest IGFBP-7 tertile conferred increased recurrence-risk in patients with IGF-IR positive tumors but not in those with IGF-IR negative tumors ( =0.024). By the 1-year visit, age-adjusted IGF-I levels were reduced by 17% while IGFBP-3 and IGFBP-7 were stable. IGF-I levels were significantly reduced by radiotherapy in all patients and by tamoxifen in patients with ER tumors. Postoperative changes >10% (n=208) in IGF-I, IGFBP-3, IGFBP-7, or the IGF-I/IGFBP-3 ratio did not predict recurrence after adjustment for preoperative levels, age, anthropometric factors, smoking, and treatments. In conclusion, this study suggests that preoperative IGF-I and IGFBP-3 levels, but not postoperative changes, might provide independent prognostic information and influence breast cancer recurrence. The role of IGFBP-7 in breast cancer merits further study.
胰岛素样生长因子-I（IGF-I）及其结合蛋白（BPs）与乳腺癌风险相关，尤其是高IGF-I浓度以及以IGF-I/IGFBP-3摩尔比估算的生物活性部分。循环IGF-I和IGFBP-3浓度与乳腺癌复发风险的关系鲜有文献记载。此外，最近在IGFBP超家族的一个亚组中发现了一个新成员，即低亲和力IGFBP-7。迄今为止，尚未研究全身性IGFBP-7在乳腺癌进展中的作用。我们的目的是确定循环IGF-I、IGFBP-3和IGFBP-7水平是否与乳腺癌复发风险相关。一项病例对照研究嵌套于瑞典基于人群的BCBlood队列中，该队列有853例2002 - 2010年诊断为乳腺癌的患者，并随访至2012年。总共95例复发患者和170例对照按年龄和肿瘤特征进行匹配。分析血浆IGF分析物和肿瘤膜IGF-I受体（IGF-IR）阳性情况，并通过条件逻辑回归评估复发风险。IGF-I和IGFBP-3术前三分位数均与复发风险呈正相关，但IGFBP-7并非如此。IGF-I的趋势具有临界显著性，T1：参考值，T2比值比：1.6，T3比值比：2.2，校正后P = 0.057；IGFBP-3具有显著性，T1：参考值，T2比值比：1.2，T3比值比：2.1，校正后P = 0.042。模型针对年龄、人体测量因素、吸烟和治疗进行了校正。IGFBP-7与IGF-IR阳性在复发方面存在显著交互作用，其中IGFBP-7最高三分位数使IGF-IR阳性肿瘤患者的复发风险增加，但IGF-IR阴性肿瘤患者并非如此（P = 0.024）。到1年随访时，年龄校正后的IGF-I水平降低了17%，而IGFBP-3和IGFBP-7保持稳定。放疗使所有患者的IGF-I水平显著降低，他莫昔芬使雌激素受体（ER）阳性肿瘤患者的IGF-I水平显著降低。在对术前水平、年龄、人体测量因素、吸烟和治疗进行校正后，IGF-I、IGFBP-3、IGFBP-7或IGF-I/IGFBP-3比值术后变化>10%（n = 208）并不能预测复发。总之，本研究表明术前IGF-I和IGFBP-3水平而非术后变化可能提供独立的预后信息并影响乳腺癌复发。IGFBP-7在乳腺癌中的作用值得进一步研究。
