University of Kansas Medical Center, University of Kansas Cancer Center, Kansas City, Kansas.
Cancer Epidemiol Biomarkers Prev. 2020 Jul;29(7):1321-1328. doi: 10.1158/1055-9965.EPI-19-1572. Epub 2020 Apr 10.
Obesity is associated with worse breast cancer prognosis, however little is known about the level of weight loss required to improve pathway biomarkers. The effects of weight regain on biomarkers are also largely unknown.
Overweight/obese breast cancer survivors enrolled in an 18-month behavioral weight loss trial provided weight and serum biomarkers [leptin, adiponectin, insulin, plasminogen activator inhibitor-1 (PAI-1), IL-6, TNFα, and hepatocyte growth factor HGF] at baseline, 6, and 18 months ( = 138). Change in biomarkers over time and by weight loss thresholds were examined.
Mean weight loss at 6 months was 13.3 ± 5.0 kg; from 6 to 18 months, mean regain was 4.0 ± 5.2 kg. Favorable biomarker modulations were observed at 6 months for leptin, adiponectin, insulin, PAI-1, IL-6, and HGF ( < 0.006 to < 0.0001). These changes remained significant overall at 18 months despite attenuation in some. Women who lost <10% of baseline weight showed significantly smaller modulation effects for leptin ( < 0.0001), adiponectin:leptin (A/L) ratio ( < 0.0001), PAI-1 ( < 0.001), and insulin ( = 0.003) compared with women who lost >10%. Women who lost >10% observed a significant increase in adiponectin ( < 0.0001), and these women continued to show improved adiponectin from 6 to 18 months despite weight regain. Physical activity contributed additional effects on biomarker change for leptin, A/L ratio, and PAI-1.
These findings are consistent with a clinical target of 10% weight.
Sustained increases in adiponectin likely confer benefits for breast cancer prognosis even with weight regain.
肥胖与乳腺癌预后较差有关，但对于改善通路生物标志物所需的减肥水平知之甚少。体重反弹对生物标志物的影响也在很大程度上尚不清楚。
超重/肥胖的乳腺癌幸存者参加了一项为期 18 个月的行为减肥试验，在基线、6 个月和 18 个月时提供体重和血清生物标志物[瘦素、脂联素、胰岛素、纤溶酶原激活物抑制剂-1（PAI-1）、白细胞介素 6（IL-6）、肿瘤坏死因子-α（TNFα）和肝细胞生长因子 HGF]（= 138）。检查了随时间和体重减轻阈值的生物标志物变化。
6 个月时的平均体重减轻量为 13.3 ± 5.0 kg；从 6 个月到 18 个月，平均增重为 4.0 ± 5.2 kg。在 6 个月时观察到瘦素、脂联素、胰岛素、PAI-1、IL-6 和 HGF 的有利生物标志物调节（<0.006 至<0.0001）。尽管在某些方面有所减弱，但这些变化在 18 个月时仍然具有统计学意义。与体重减轻<10%的基线体重相比，体重减轻<10%的女性，瘦素（<0.0001）、脂联素与瘦素的比值（<0.0001）、PAI-1（<0.001）和胰岛素（=0.003）的调节作用明显较小。体重减轻>10%的女性观察到脂联素显著增加（<0.0001），并且这些女性在体重增加的情况下，从 6 个月到 18 个月继续表现出脂联素的改善。体力活动对瘦素、脂联素与瘦素比值和 PAI-1 的生物标志物变化有额外的影响。
这些发现与 10%的体重目标一致。
即使体重增加，脂联素的持续增加也可能为乳腺癌的预后带来益处。
