Comparison of efficacy of 95-gene and 21-gene classifier (Oncotype DX) for prediction of recurrence in ER-positive and node-negative breast cancer patients

We recently developed a 95-gene classifier (95^GC) for the prognostic prediction for ER-positive and node-negative breast cancer patients treated with only adjuvant hormonal therapy. The aim of this study was to validate the efficacy of 95^GC and compare it with that of 21^GC (Oncotype DX) as well as to evaluate the combination of 95^GC and 21^GC. DNA microarray data (gene expression) of ER-positive and node-negative breast cancer patients (n = 459) treated with adjuvant hormone therapy alone as well as those of ER-positive breast cancer patients treated with neoadjuvant chemotherapy (n = 359) were classified with 95^GC and 21^GC (Recurrence Online at http://​www.​recurrenceonline​.​com/​). 95^GC classified the 459 patients into low-risk (n = 285; 10 year relapse-free survival: 88.8 %) and high-risk groups (n = 174; 70.6 %) (P = 5.5e−10), and 21^GC into low-risk group (n = 286; 89.3 %), intermediate-risk (n = 81; 75.7 %), and high-risk (n = 92; 64.7 %) groups (P = 2.9e−10). The combination of 95^GC and 21^GC classified them into low-risk (n = 324; 88.9 %) and high-risk (n = 135; 65.0 %) groups (P = 5.9e−14), and also showed that pathological complete response rates were significantly (P = 2.5e−6) higher for the high-risk (17.9 %) than the low-risk group (3.6 %). In addition, we demonstrated that 95^GC was calculated on a single-sample basis if the reference robust multi-array average workflow was used for normalization. The prognostic prediction capability of 95^GC appears to be comparable to that of 21^GC. Moreover, their combination seems to result in the identification of more low-risk patients who do not need chemotherapy than either classification alone. The patients in the high-risk group were found to be more chemo-sensitive so that they can benefit more from adjuvant chemotherapy.