Tong Yiwei, Wu Jiayi, Huang Ou, He Jianrong, Zhu Li, Chen Weiguo, Li Yafen, Chen Xiaosong, Shen Kunwei
Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Oncol. 2020 Apr 24;10:550. doi: 10.3389/fonc.2020.00550. eCollection 2020.
Dysmetabolism and high circulating insulin-like growth factor 1 (IGF-1) would increase breast cancer risk, but its association with survival in HER2+ breast cancer patients has not been well-studied. Herein, we aim to evaluate the prognostic value of IGF-1 and metabolic abnormalities in HER2+ population. HER2+ breast cancer patients treated in Ruijin Hospital between November 2012 and June 2017 were retrospectively analyzed. Median value of circulating IGF-1 was adopted to classify low or high IGF-1 group. Metabolic syndrome (MetS) was defined using AHA/NHLBI criteria. Overweight was defined by body mass index (BMI) ≥ 24.0 kg/m in Chinese population. Overall, 679 patients were included and 209 had synchronous MetS. High IGF-1 level was more common in pre/peri-menopausal women ( < 0.001) and high IGFBP-3 patients ( < 0.001). After a median follow-up of 36 months, 52 patients had disease recurrences. IGF-1 level was not associated with recurrence-free survival (RFS, = 0.620) in the whole population. However, exploratory subgroup analysis found that BMI and IGF-1 interacted in predicting RFS ( = 0.009). For non-overweight patients, high IGF-1 showed a superior 4-years RFS (91.1 vs. 85.0%; HR 0.53, 95% CI 0.27-1.00, = 0.049) compared with patients with low IGF-1 level. In contrast, for overweight patients, high IGF-1 was associated with an impaired 4-years RFS (88.3 vs. 95.7%, HR 3.20, 95% CI 1.00-10.21, = 0.038). Furthermore, high IGF-1 level was independently associated with better OS in the whole (HR 0.26, 95% CI 0.08-0.82, = 0.044) as well as non-overweight population (HR 0.15, 95% CI 0.03-0.68, = 0.005). IGF-1 level was not associated with RFS in HER2+ breast cancer patients. However, IGF-1 and BMI had significant interaction in disease outcome prediction in HER2+ patients. High IGF-1 was protective in non-overweight patients, but risk factor for those overweight, which deserves further evaluation.
代谢紊乱和循环胰岛素样生长因子1(IGF-1)水平升高会增加患乳腺癌的风险,但其与HER2+乳腺癌患者生存情况的关联尚未得到充分研究。在此,我们旨在评估IGF-1和代谢异常在HER2+人群中的预后价值。对2012年11月至2017年6月在瑞金医院接受治疗的HER2+乳腺癌患者进行回顾性分析。采用循环IGF-1的中位数将患者分为IGF-1水平低或高的组。代谢综合征(MetS)根据美国心脏协会/美国国立卫生研究院心肺血液研究所(AHA/NHLBI)标准定义。在中国人群中,超重定义为体重指数(BMI)≥24.0kg/m²。总体而言,共纳入679例患者,其中209例同时患有代谢综合征。IGF-1水平高在绝经前/围绝经期女性(P<0.001)和IGFBP-3水平高的患者中更常见(P<0.001)。中位随访36个月后,52例患者出现疾病复发。在整个人群中,IGF-1水平与无复发生存期(RFS,P=0.620)无关。然而,探索性亚组分析发现,BMI和IGF-1在预测RFS方面存在相互作用(P=0.009)。对于非超重患者,与IGF-1水平低的患者相比,IGF-1水平高的患者4年无复发生存率更高(91.1%对85.0%;风险比[HR]0.53,95%置信区间[CI]0.27-1.00,P=0.049)。相反,对于超重患者,IGF-1水平高与4年无复发生存率受损相关(88.3%对95.7%,HR3.20,95%CI1.00-10.21,P=0.038)。此外,在整个人群(HR0.26,95%CI0.08-0.82,P=0.044)以及非超重人群中(HR0.15,95%CI0.03-0.68,P=0.005),IGF-1水平高与更好的总生存期独立相关。在HER2+乳腺癌患者中,IGF-1水平与RFS无关。然而,IGF-1和BMI在HER2+患者疾病结局预测中存在显著相互作用。IGF-1水平高对非超重患者具有保护作用,但对超重患者是危险因素,这值得进一步评估。