Risk assessment after neoadjuvant chemotherapy in luminal breast cancer using a clinico-molecular predictor

Purpose: This study aimed to evaluate a modified EPclin test (mEPclin), a combination of EndoPredict (EP) score, post-neoadjuvant pathological tumor size and nodal status, for predicting the risk of distance recurrence after neoadjuvant chemotherapy (NACT) in patients with residual estrogen-receptor (ER)-positive/HER2-negative breast cancer (BC). We also compared the prognostic power of the mEPclin with that of the CPS-EG score. Experimental Design: 428 formalin-fixed, paraffin-embedded tumor samples from GeparTrio and GeparQuattro studies were evaluated for mRNA expression of eight cancer-related and three reference genes. The mEPclin score was computed using a modified algorithm and predefined cutoff values were used to classify each patient at low or high risk. Primary endpoint was disease-free survival (DFS). Results: A higher continuous mEPclin score was significantly associated with increased risk of relapse (HR=2.16 [95%CI 1.86-2.51]; p<0.001) and death (HR=2.28 [95% CI 1.90-2.75]; p<0.001). Similarly, patients classified at high risk by dichotomous mEPclin showed significantly poorer disease-free and overall survival compared to those at low risk. In contrast to CPS-EG, the mEPclin remained significantly prognostic for DFS in multivariate analysis (HR=2.13 [1.73-2.63]; p<0.001). Combining CPS-EG and other clinicopathological variables with mEPclin yielded a significant improvement of the prognostic power for DFS versus without mEPclin (c-indices: 0.748 vs. 0.660; p<0.001). Conclusions: The mEPclin score independently predicted the risk of distance recurrence and provided additional prognostic information to the CPS-EG score to assess more accurately the prognosis after NACT in the luminal non-pCR patient population. Therefore, this approach can be used to select patients for additional post-neoadjuvant therapies.

https://ift.tt/2q6pM9A