The impact of the 21-gene Recurrence Score assay on clinical decision-making in node-positive (up to 3 positive nodes) estrogen receptor-positive breast cancer patients

Abstract

Oncotype DX testing is reimbursed in Israel for node-negative and node-positive (N1+; up to 3 positive nodes including micrometastases), estrogen receptor positive (ER+), breast cancer patients. This retrospective study evaluated the impact of Oncotype DX testing on treatment decisions in N1+/ER+ breast cancer patients. To this end, we compared treatments for all N+ patients for whom testing had been ordered with treatments for patients with similar characteristics where the test had not been available. The retrospective analysis included 951 patients (282 Oncotype DX, 669 controls), all of whom received endocrine therapy with or without chemotherapy. In Oncotype DX patients, 7.1, 37.0, and 100 % of those with low, intermediate, and high Recurrence Score results (Oncotype DX summary score) received chemotherapy, respectively (P < 0.0001, all comparisons). Chemotherapy use was lower in Oncotype DX patients versus controls (24.5 vs. 70.1 %). In a multivariate logistic regression analysis in which the probability of receiving chemotherapy was modeled as a function of Oncotype DX testing, age, tumor size, tumor grade, nodal status, and the interactions between Oncotype DX testing and the other covariates, Oncotype DX testing was associated with significantly lower odds of receiving chemotherapy (odds ratio 0.16; 95 % CI 0.11–0.24; P < 0.0001). In summary, our findings suggest that Oncotype DX testing has a significant impact on reducing chemotherapy use in N1+/ER+ breast cancer patients in Israel.

Association of survivin splice variants with prognosis and treatment of breast cancer

“…Only patients belonging to the high Recurrence Score group were prescribed for chemotherapy. The differences in the proportions of patients treated with chemotherapy between the low, intermediate, and high Recurrence Score groups were statistically significant [32] . The clinical application of Oncotype DX testing was correlated with a decrease in chemotherapy and change of treatment recommendations [32] .…”

“…The differences in the proportions of patients treated with chemotherapy between the low, intermediate, and high Recurrence Score groups were statistically significant [32] . The clinical application of Oncotype DX testing was correlated with a decrease in chemotherapy and change of treatment recommendations [32] . In another recent study, Solin et al [33] 2013 used the so-called 12-gene Oncotype DX DCIS Score, which quantifies local recurrence risk and provides risk information independent of traditional clinical and pathologic characteristics.…”

“…Other commercial kits employ RT-PCR assays for selected genes from RNA extracted from formalin-fixed paraffin-embedded tissues: (1) an 8-gene panel from Aviara (now Biotheranostics Inc) combining the Breast Cancer Index HOXB13:IL17BR ratio with the Molecular Grade Index consisting of the average expression of five cell cycle-associated genes (BUB1B, CENPA, NEK2, RACGAP1 and RRM2) [29] ; (2) the PAM 50 assay (by ARUP Laboratories) that includes wild-type survivin among the 50 selected genes [30] ; and (3) the FDAapproved Oncotype DX Breast Cancer Assay (by Genomic Health). Oncotype DX testing may aid a patient by preventing redudant chemotherapy and its connected toxicity, while reduction of chemotherapy also leads to economical changes in health systems [31,32] . It provides breast cancer patients with a Recurrence Score (RS) (a number between 0 and 100) that corresponds to a specific likelihood of breast cancer recurrence within 10 years of the initial diagnosis.…”

“…A low risk of recurrence is defined of less than 18, an intermediate risk as less than 31 and a high risk as 31 and higher. In Stemmer's et al [32] 2013 article, Oncotype DX testing seems to have significant impact on minimising chemotherapy in node positive/estrogen positive (N1+/ ER+) patients with breast tumor. It has been proven that Recurrence Score is correlated with tumor grade; higher Recurrence Score results are associated with higher histologic grade.…”

Gene Expression Profiling in Breast Cancer and Its Effect on Therapy Selection in Early-Stage Breast Cancer

“…It was seen that CT was beneficial in distinguishing nodepositive patients who would benefit from CT (Predictor of likelihood of chemotherapy benefit in ER+ Node positive disease). Its prospective validation in the node-positive patients was demonstrated in the West German Study Group Plan B Randomized Phase-3 study, the Clalit Registry study conducted in Israel and the SEER real-life observational study (31)(32)(33). In all these studies, the 5-year survival rate of patients in the low risk group is >95%.…”