Monitoring Serum VEGF in Neoadjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer: A New Strategy for Early Prediction of Treatment Response and Patient Survival

This study aimed to investigate the clinical utility of serum biomarker changes during neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC).

Our findings indicate that monitoring serum VEGF could help identify patients with different responses at an early time point of NAC and at varying risk of disease relapse. Serum VEGF may also serve as an alternative to traditional response-evaluating methodologies in tailoring and modifying the NAC strategy for both operable and advanced TNBCs. Implications for practice: Neoadjuvant chemotherapy (NAC) followed by definitive surgery is a standard of care for locally advanced breast cancer. The identification of sensitive responders to neoadjuvant therapy is highly significant for breast cancer, especially triple-negative breast cancer (TNBC). Results of this study indicate that the monitoring of serum vascular endothelial growth factor (VEGF) could identify patients with favorable or poor responses at an early time point of NAC. Furthermore, the prediction power of VEGF was better than traditional response-evaluating methods. VEGF might serve as a complement or alternative to traditional imaging-based response-evaluating methodologies in tailoring systemic treatment strategies for both operable and advanced TNBCs. 摘要 背景。本研究旨在调查血清生物标志物变化在三阴性乳腺癌 (TNBC) 的新辅助化疗 (NAC) 期间的临床实用性。 方法。本研究一共包含 303 名 TNBC 患者。我们在 NAC 期间的 3 个时间点采集血清样本:基线、第 3 个周期之前以及手术之前。我们使用针对 29 个血清生物标志物的 Luminex 多生物标志物组来检测它们与 NAC 缓解的相关性。然后，我们研究了每个选定的生物标志物的预测和预后价值。 结果。血管内皮生长因子 (VEGF) 是与治疗反应相关的唯一生物标志物，相对于非 pCR 患者而言，在 pCR 患者中呈现下降的趋势(p < 0.001)。单变量和多变量分析显示，在 NAC 的第 3 个周期之前 VEGF 的相对变化对于 pCR 和病理无缓解而言具有重要的预测价值，且具有高度敏感性和特异性。VEGF 也与无病生存期独立相关。 结论。我们的研究结果表明，监测血清 VEGF 有助于在 NAC 的早期时间点以及在不同的疾病复发风险情况下确定具有不同反应的患者。在制定和修改针对可手术的 TNBC 及晚期 TNBC 的 NAC 策略时，血清 VEGF 还可以作为传统缓解评估方法的替代选择。 对临床实践的提示:在新辅助化疗 (NAC) 之后进行根治性手术是局部晚期乳腺癌的标准治疗方案。就乳腺癌而言，尤其是三阴性乳腺癌 (TNBC)，识别新辅助治疗的敏感缓解者非常重要。本研究结果表明，监测血清血管内皮生长因子 (VEGF) 可以在 NAC 的早期时间点识别具有良好反应或不良反应的患者。此外，VEGF 的预测能力比传统的缓解评估方法更好。在制定针对可手术的 TNBC 及晚期 TNBC 的系统治疗策略时，VEGF 可以作为基于图像的传统缓解评估方法的补充或替代选择。

A total of 303 patients with TNBC were included in this study. Serum samples were taken at three time points during NAC: baseline, prior to the third cycle, and prior to surgery. Luminex multibiomarker panel for 29 serum biomarkers was used to detect their correlation with NAC response. The predictive and prognostic value of each selected biomarker was then studied.

Vascular endothelial growth factor (VEGF) was the only biomarker that correlated with treatment response, with a decreasing trend in pCR patients relative to non-pCR patients (p < .001). Univariable and multivariable analyses revealed that the relative change in VEGF prior to the third cycle of NAC had a remarkable predictive value for both pCR and pathological nonresponse with high sensitivity and specificity. VEGF was also independently correlated with disease-free survival.