Department of Breast Surgery, Fudan University Shanghai Cancer Center/Cancer Institute, 399 Ling-Ling Road, Shanghai, 200032, People's Republic of China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
BMC Cancer. 2018 Sep 21;18(1):909. doi: 10.1186/s12885-018-4822-7.
This study aimed to investigate the clinical utility of serum and histological MMP-9 detection during neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC).
A total of 303 TNBC patients who underwent weekly paclitaxel plus carboplatin treatments followed by surgical resection were included in this study. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum level of Matrix metalloproteinase-9 (sMMP-9) at baseline and prior to surgery. Immunohistochemistry was used to detect histological MMP-9 (hMMP-9) expression in patients with residual tumors after NAC. The value of MMP-9 to predict the response to NAC and patient survival was studied.
Of the 303 patients, 103 (34.0%) patients experienced pathological complete response (pCR) after completion of NAC. Univariate and multivariate analyses revealed that the relative change in sMMP-9, rather than sMMP-9 at baseline or surgery, had a remarkable predictive value for pCR. Each 1 ng/ml decrease in sMMP-9 after NAC was shown to result in a 0.3% increase in pCR rate. Additionally, in survival analyses, hMMP-9 expression in residual tumors was independently correlated with disease-free survival for non-pCR responders (P < 0.001).
Our findings indicate that monitoring serum MMP-9 and detection of histological MMP-9 could help identify TNBC patients who will respond to NAC and will display varying risks of disease relapse. MMP-9 may serve as a predictive and prognostic biomarker for tailoring and modifying the NAC strategy for TNBC.
本研究旨在探讨 MMP-9 检测在三阴性乳腺癌(TNBC)新辅助化疗(NAC)中的临床应用价值。
共纳入 303 例接受每周紫杉醇联合卡铂治疗后行手术切除的 TNBC 患者。采用酶联免疫吸附试验(ELISA)检测基线和术前血清基质金属蛋白酶-9(sMMP-9)水平,采用免疫组化法检测 NAC 后残留肿瘤组织中 MMP-9 的表达,研究 MMP-9 对预测 NAC 反应和患者生存的价值。
303 例患者中,103 例(34.0%)患者在 NAC 完成后获得病理完全缓解(pCR)。单因素和多因素分析表明,sMMP-9 的相对变化,而不是基线或手术时的 sMMP-9,对 pCR 有显著的预测价值。NAC 后 sMMP-9 每降低 1ng/ml,pCR 率增加 0.3%。此外,在生存分析中,非 pCR 反应者残留肿瘤中 hMMP-9 的表达与无病生存独立相关(P<0.001)。
我们的研究结果表明,监测血清 MMP-9 和检测组织学 MMP-9 可以帮助识别对 NAC 有反应的 TNBC 患者,并显示出不同的疾病复发风险。MMP-9 可能成为 TNBC 患者 NAC 个体化和调整治疗策略的预测和预后生物标志物。