Implications of the 21-gene recurrence score assay (Oncotype DX) on adjuvant treatment decisions in ER-positive early-stage breast cancer patients: experience of Kuwait Cancer Control Center

Abstract

Background: The Oncotype DX is a quantitative assay of the expression of 16 tumor-related genes and 5 reference genes that predicts the potential of adjuvant chemotherapy benefit in estrogen receptor (ER)-positive early breast cancer patients. The study aims to evaluate the impact of Oncotype DX as a tool for adjuvant treatment decision of ER-positive, HER2-negative, N0/N1 early-stage breast cancer patients and to determine which clinicopathological criteria derived the greatest advantage. Results: A hundred patients at a median age of 50 years were included. TNM stage distribution was 34, 63, and 3 patients for stages I, II, and IIIA respectively. Fifty-four patients had luminal A and 46 had luminal B tumors. The recurrence score (RS) results were low, intermediate, and high risk in 54, 34, and 12 patients respectively. Before the test results, adjuvant chemoendocrine therapy (CET) was recommended for 46 patients while 54 were advised for endocrine therapy (ET). After getting the test results, 25 patients received CET (1, 12, and12 patients in the low-, intermediate-, and high-risk groups respectively) and 75 received ET. Treatment change was documented in 37 patients (8 patients from ET to CET and 29 from CET to ET; p = 0.001, McNemar test). Treatment change was significant among patients ≤ 50 years, luminal B tumors, stage II and IIIA disease, and node-positive disease. Conclusion: Oncotype DX testing resulted in significant changes in the adjuvant treatment decisions in ER-positive, HER2-negative early breast cancer particularly in the case of young, luminal B, N1, and stage II-IIIA disease.

The Level of Agreement Among Medical Oncologists on Adjuvant Chemotherapy Decision for Breast Cancer in Pre and Post-Oncotype DX Settings

“…Studies have reported that the ODx RS does not only predict the RR but can also predict mortality independently of other covariates [11]. In line with our findings, a recent study also reported an impact of the assay on AC decision, leading to a change in the decision of omitting chemotherapy in 37% of the cases where chemotherapy was recommended pre-ODx, and in 14.8% of the cases where chemotherapy was prescribed after the decision was changed to yes to chemotherapy from an initial decision of a norecommendation [24]. Compared to our study they reported a higher percentage of patients with a change in the decision for both groups.…”

“…In other words, the change to a decision of chemotherapy administration was less frequent than the change to a decision of omitting chemotherapy. This is consistent with those reported in the region as well as internationally [1,24,25]. Rizki et al also reported that the precision of the ODx score in guiding the decision to use AC is much superior to other clinicopathological tools [26].…”

“…The mean ODx recurrence score of our cohort was 17.8 ± 8.6. Categorical distribution of the RS revealed 79 cases (54.5%) had low-risk (0-17), 55 (37.9%) had intermediate-risk (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), and only 11 (7.6%) had high-risk (31-100). The progesterone receptor was positive in 139 cases (95.9%) and negative in only six cases (4.1%).…”

“…The descriptive statistics were given as mean ± SD or median with quartiles for numerical variables and as frequencies and percentages for categorical variables. In the analysis, the ODx risk scores were used as continuous variables as well as based on old RS grouping, categorized into low (0-17), intermediate (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), and high risk (≥ 31) groups. Microsoft Excel and IBM SPSS Statistics for Windows, Version 22.0 (IBM Corp., Armonk, NY) was used for data entry and analysis.…”

“…It provides a continuous numeric recurrence score (RS) ranging from 0 to 100 or divided into low (0-17), intermediate (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), and high scores (≥ 31) [8]. The recent TAILORx data redefined these risk categories for < 50 years old patients into low risk (< 16), intermediate (16)(17)(18)(19)(20)(21)(22)(23)(24)(25), and high-risk groups (> 25) [10]. The 21 genes assay includes 16 cancer genes subdivided into five proliferative genes (Ki67, STK15, Survivin, CCNB1, and MYBL2), five estrogen receptor (ER) genes (ER, PGR, BCL2, and SCUBE2), two HER2 genes (HER2 and GRB7), two invasive genes (MMP11 and CTSL2), and one gene from GTSM1; and remaining five reference genes including B-Actin, GAPDH, RPLPO, TFRC, and GUS genes.…”