Development of recurrence risk score using 95-gene classifier and its application to formalin-fixed paraffin-embedded tissues in ER-positive, HER2-negative and node-negative breast cancer

We previously developed a 95-gene classifier (95GC) to classify ER-positive/HER2-negative/node-negative (ER+/HER2(-)/N0) breast cancer as high- and low-risk. The present study aimed to devise a 95GC recurrence score ((RS)-R-95GC) to estimate recurrence risk more precisely and, although the 95GC was originally developed using fresh-frozen (FF) tissues, this was applied to formalin-fixed paraffin-embedded (FFPE) tissues. (RS)-R-95GC was calculated using between-group analysis and denominated as a value from 0 to 100. Correlation of (RS)-R-95GC with distant recurrence rate and response to neoadjuvant chemotherapy (NAC) was evaluated in 257 patients with ER+/HER2(-)/N0 breast cancer treated with adjuvant hormonal therapy at Osaka University Hospital and in 425 patients with ER+ breast cancer treated with NAC at Osaka University Hospital and the University of Texas MD Anderson Cancer Center (GSE25066 dataset). Correlation of (RS)-R-95GC between FF and FFPE tissues was evaluated in paired tissues from 56 ER+/HER2(-)/N0 breast cancer types obtained from patients without NAC treatment. Distant recurrence rates were remarkably low in patients with (RS)-R-95GC <= 50 and increased proportionally in patients with (RS)-R-95GC >50. Pathological complete response (pCR) rates to NAC were increased in proportion to (RS)-R-95GC, indicating a greater sensitivity of breast cancers with high (RS)-R-95GC to chemotherapy. (RS)-R-95GC was highly correlated (R=0.92) between FF and FFPE tissues, and the concordance rate (94.6%) of high- and low-risk groups was also considerably high. Overall, the present study developed a (RS)-R-95GC that correlated with distant recurrence rate and pCR rate to NAC. The 95GC was applicable to FFPE tissues with a high concordance rate in FF tissues.