A Novel Immunomodulatory 27-Gene Signature to Predict Response to Neoadjuvant Immunochemotherapy for Primary Triple-Negative Breast Cancer

Simple Summary Through analysis of specimens from patients with primary triple-negative breast cancer (TNBC) enrolled in a neoadjuvant clinical trial assessing durvalumab with chemotherapy, we confirmed a novel 27-gene immuno-oncology (IO) signature that generates an IO score to predict the pathologic complete response (pCR) of primary TNBC to neoadjuvant immunotherapy with the PD-L1 blocker durvalumab with chemotherapy. Combining the 27-gene IO signature with PD-L1 immunohistochemistry strengthened the model's predictive power of the pCR. Furthermore, the comprehensive computational analysis revealed that the 27-gene IO signature corresponded with an immunogenic tumor microenvironment. A precise predictive biomarker for TNBC response to immunochemotherapy is urgently needed. We previously established a 27-gene IO signature for TNBC derived from a previously established 101-gene model for classifying TNBC. Here we report a pilot study to assess the performance of a 27-gene IO signature in predicting the pCR of TNBC to preoperative immunochemotherapy. We obtained RNA sequencing data from the primary tumors of 55 patients with TNBC, who received neoadjuvant immunochemotherapy with the PD-L1 blocker durvalumab. We determined the power and accuracy in predicting pCR for the immunomodulatory (IM) subtype identified by the 101-gene model, the 27-gene IO signature, and PD-L1 expression by immunohistochemistry (IHC). The pCR rate was 45% (25/55). The odds ratios for pCR were as follows: IM subtype by 101-gene model, 3.14 (p = 0.054); 27-gene IO signature, 4.13 (p = 0.012); PD-L1 expression by IHC, 2.63 (p = 0.106); 27-gene IO signature in combination with PD-L1 expression by IHC, 6.53 (p = 0.003). The 27-gene IO signature has the potential to predict the pCR of primary TNBC to neoadjuvant immunochemotherapy. Further analysis in a large cohort is needed.

Automated summary

The study confirmed a novel 27-gene immuno-oncology signature for predicting the pathologic complete response of primary triple-negative breast cancer to neoadjuvant immunotherapy. Combining this signature with PD-L1 immunohistochemistry enhanced the predictive power. Further analysis in a larger cohort is warranted.