Abstract
<div>AbstractPurpose:<p>Caveolin-1 and -2 (<i>CAV1/2</i>) dysregulation are implicated in driving cancer progression and may predict response to nab-paclitaxel. We explored the prognostic and predictive potential of <i>CAV1/2</i> expression for patients with early-stage HER2-negative breast cancer receiving neoadjuvant paclitaxel-based chemotherapy regimens, followed by epirubicin and cyclophosphamide.</p>Experimental Design:<p>We correlated tumor <i>CAV1/2</i> 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.</p>Results:<p>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 <i>CAV1/2</i> had higher probability of obtaining a pCR [<i>CAV1</i> OR, 4.92; 95% confidence interval (CI), 1.70–14.22; <i>P</i> = 0.003; <i>CAV2</i> OR, 5.39; 95% CI, 1.76–16.47; <i>P</i> = 0.003] as compared with patients with high <i>CAV1/2</i> treated with solvent-based paclitaxel (<i>CAV1</i> OR, 0.33; 95% CI, 0.11–0.95; <i>P</i> = 0.040; <i>CAV2</i> OR, 0.37; 95% CI, 0.12–1.13; <i>P</i> = 0.082). High <i>CAV1</i> expression was significantly associated with worse DFS and OS in paclitaxel-treated patients (DFS HR, 2.29; 95% CI, 1.08–4.87; <i>P</i> = 0.030; OS HR, 4.97; 95% CI, 1.73–14.31; <i>P</i> = 0.003). High <i>CAV2</i> was associated with worse DFS and OS in all patients (DFS HR, 2.12; 95% CI, 1.23–3.63; <i>P</i> = 0.006; OS HR, 2.51; 95% CI, 1.22–5.17; <i>P</i> = 0.013), in paclitaxel-treated patients (DFS HR, 2.47; 95% CI, 1.12–5.43; <i>P</i> = 0.025; OS HR, 4.24; 95% CI, 1.48–12.09; <i>P</i> = 0.007) and in patients with TNBC (DFS HR, 4.68; 95% CI, 1.48–14.85; <i>P</i> = 0.009; OS HR, 10.43; 95% CI, 1.22–89.28; <i>P</i> = 0.032).</p>Conclusions:<p>Our findings indicate high <i>CAV1/2</i> expression is associated with worse DFS and OS in paclitaxel-treated patients. Conversely, in nab-paclitaxel–treated patients, high <i>CAV1/2</i> expression is associated with increased pCR and no significant detriment to DFS or OS compared with low <i>CAV1/2</i> expression.</p></div>
Published Version
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