背景:Caveolin-1和-2(CAV1/2)失调与驱动癌症进展有关,并可能预测对nab-紫杉醇的反应。我们探讨了CAV1/2表达对接受基于紫杉醇的新辅助化疗方案的早期HER2阴性(HER-)乳腺癌(BC)患者的预后和预测潜力。
方法:我们将肿瘤CAV1/2RNA表达与病理完全反应(pCR)相关联,GeparSepto试验中的无病生存期(DFS)和总生存期(OS),将患者随机分配到以紫杉醇为基础的新辅助化疗。
结果:有279例患者的RNA-Seq数据,其中74例(26.5%)为激素受体(HR)阴性,因此三阴性BC(TNBC)。与接受溶剂型紫杉醇治疗的高CAV1/2患者相比,接受nab-紫杉醇治疗的患者获得pCR的可能性更高(CAV1比值比(OR)=4.92,95%CI1.70-14.22,p=0.003;CAV2OR=5.39,95CI1.76-16.47,p=0.003)。在紫杉醇治疗的患者中,高CAV1表达与DFS和OS恶化显著相关(DFSHR=2.29,95CI1.08-4.87,p=0.030;OSHR=4.97,95CI1.73-14.31,p=0.003)。高CAV2与所有患者的DFS和OS恶化相关(DFSHR=2.12,p=0.006;OSHR=2.51,p=0.013),紫杉醇治疗患者(DFSHR=2.47,p=0.025;OSHR=4.24,p=0.007)和TNBC患者(DFSHR=4.68,p=0.009;OSHR=10.43,p=0.032).
结论:我们的研究结果表明,在紫杉醇治疗的患者中,高CAV1/2表达与较差的DFS和OS相关。相反,在nab-紫杉醇治疗的患者中,与低CAV1/2表达相比,高CAV1/2表达与pCR增加相关,对DFS或OS没有显著损害。
Caveolin-1 and -2 (CAV1/2) dysregulation are implicated in driving cancer progression and may predict response to nab-paclitaxel. We explored the prognostic and predictive potential of CAV1/2 expression for patients with early-stage HER2-negative breast cancer receiving neoadjuvant paclitaxel-based chemotherapy regimens, followed by epirubicin and cyclophosphamide.
We correlated tumor CAV1/2 RNA expression with pathologic complete response (pCR), disease-free survival (DFS), and overall survival (OS) in the GeparSepto
trial, which randomized patients to neoadjuvant paclitaxel- versus nab-paclitaxel-based chemotherapy.
RNA sequencing data were available for 279 patients, of which 74 (26.5%) were hormone receptor (HR)-negative, thus triple-negative breast cancer (TNBC). Patients treated with nab-paclitaxel with high CAV1/2 had higher probability of obtaining a pCR [CAV1 OR, 4.92; 95% confidence interval (CI), 1.70-14.22; P = 0.003; CAV2 OR, 5.39; 95% CI, 1.76-16.47; P = 0.003] as compared with patients with high CAV1/2 treated with solvent-based paclitaxel (CAV1 OR, 0.33; 95% CI, 0.11-0.95; P = 0.040; CAV2 OR, 0.37; 95% CI, 0.12-1.13; P = 0.082). High CAV1 expression was significantly associated with worse DFS and OS in paclitaxel-treated patients (DFS HR, 2.29; 95% CI, 1.08-4.87; P = 0.030; OS HR, 4.97; 95% CI, 1.73-14.31; P = 0.003). High CAV2 was associated with worse DFS and OS in all patients (DFS HR, 2.12; 95% CI, 1.23-3.63; P = 0.006; OS HR, 2.51; 95% CI, 1.22-5.17; P = 0.013), in paclitaxel-treated patients (DFS HR, 2.47; 95% CI, 1.12-5.43; P = 0.025; OS HR, 4.24; 95% CI, 1.48-12.09; P = 0.007) and in patients with TNBC (DFS HR, 4.68; 95% CI, 1.48-14.85; P = 0.009; OS HR, 10.43; 95% CI, 1.22-89.28; P = 0.032).
Our findings indicate high CAV1/2 expression is associated with worse DFS and OS in paclitaxel-treated patients. Conversely, in nab-paclitaxel-treated patients, high CAV1/2 expression is associated with increased pCR and no significant detriment to DFS or OS compared with low CAV1/2 expression.