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

Abstract

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.

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

“…The 95GC helps classify patients with ER + /HER2-/N0 breast cancer types into high-and low-risk groups. In addition, intermediate risk breast cancer types [recurrence score (RS), 18-30] classified using 21GC ( 21GC RS were calculated using Recurrence Online) can be further dichotomized using a 95GC into low-and high-risk groups (5). This dichotomization is expected to lead to a significant difference in disease prognosis, suggesting the use of 95GC in predicting the prognosis of intermediate-risk breast cancers.…”

Endocrine sensitivity of estrogen receptor‐positive breast cancer is negatively correlated with aspartate‐β‐hydroxylase expression

“…Recent advances in multiple gene expression assays have enabled the classification of ER‐positive breast cancer into favorable and unfavorable prognoses. Representative examples of gene expression assays are Oncotype DX, MammaPrint, and Curebest 95GC, which were developed to detect patient subpopulations that do not require adjuvant chemotherapy. Moreover, Prediction Analysis of Microarray 50 (PAM50) which classifies breast cancer into five intrinsic subtypes (luminal A, luminal B, receptor tyrosine protein kinase ERBB2 [HER2]‐enriched, claudin‐low, and basal‐like) based on their biological and histological characteristics, is widely used, as each identifiable subtype has a distinct prognosis and distinct therapeutic strategy, and clinical markers, including ER, PR, HER2, and Ki‐67 can be used as surrogate markers to classify breast cancer types .…”

<p>Decision of Adjuvant Systemic Treatment in HR+ HER2- Early Invasive Breast Cancer: Which Biomarkers Could Help?</p>

“…Several retrospective studies using archived samples from prospective studies found a difference of DFS between the 3 RS groups in a large population of ER+ patients (n=3382), pN031,34–36 or pN+ 37–39. Other retrospective studies found similar results in a mostly ER+ population40–45 ( Table S2 , in supplementary data). Most studies showed a significant association between Oncotype DX ® and breast cancer outcome: in ER+ pN0 patients without systemic treatment,46 in ER+ pN0 patients treated with ET alone,31,36,40,42,44–47 and in patients treated with chemotherapy and ET 34,41,43,46,48.…”