Low RNA disruption during neoadjuvant chemotherapy predicts pathologic complete response absence in patients with breast cancer

Abstract

In previously reported retrospective studies, high tumor RNA disruption during neoadjuvant chemotherapy predicted for post-treatment pathologic complete response (pCR) and improved disease-free survival at definitive surgery for primary early breast cancer. The BREVITY (Breast Cancer Response Evaluation for Individualized Therapy) prospective clinical trial (NCT03524430) seeks to validate these prior findings. Here we report training set (Phase I) findings, including determination of RNA disruption index (RDI) cut points for outcome prediction in the subsequent validation set (Phase II; 454 patients). In 80 patients of the training set, maximum tumor RDI values for biopsies obtained during neoadjuvant chemotherapy were significantly higher in pCR responders than in patients without pCR post-treatment (P = .008). Moreover, maximum tumor RDI values ≤3.7 during treatment predicted for a lack of pCR at surgery (negative predictive value = 93.3%). These findings support the prospect that on-treatment tumor RNA disruption assessments may effectively predict post-surgery outcome, possibly permitting treatment optimization.

Figure 1.

A) Plot of negative predictive value (NPV) for pathologic complete response (pCR) calculated for each maximum RNA disruption index (RDI) value; Zone 1 defines patients with maximum RDI values ≤3.7. B) Plot of positive predictive value (PPV) for pCR for each maximum RDI value; Zone 3 defines patients with maximum RDI values >10.0.