Adjuvant treatment recommendations for patients with ER-positive/HER2-negative early breast cancer by Swiss tumor boards using the 21-gene recurrence score (SAKK 26/10)

Abstract

BackgroundTo evaluate the effect of Recurrence Score® results (RS; Oncotype DX® multigene assay ODX) on treatment recommendations by Swiss multidisciplinary tumor boards (TB).MethodsSAKK 26/10 is a multicenter, prospective cohort study of early breast cancer patients: Eligibility: R0-resection, ≥10% ER+ malignant cells, HER2–, pN0/pN1a. Patients were stratified into low-risk (LR) and non-low-risk (NLR) groups based on involved nodes (0 vs 1–3) and five additional predefined risk factors. Recommendations were classified as hormonal therapy (HT) or chemotherapy plus HT (CT + HT). Investigators were blinded to the statistical analysis plan. A 5%/10% rate of recommendation change in LR/NLR groups, respectively, was assumed independently of RS (null hypotheses).ResultsTwo hundred twenty two evaluable patients from 18 centers had TB recommendations before and after consideration of the RS result. A recommendation change occurred in 45 patients (23/154 (15%, 95% CI 10–22%) in the LR group and 22/68 (32%, 95% CI 22–45%) in the NLR group). In both groups the null hypothesis could be rejected (both p < 0.001). Specifically, in the LR group, only 5/113 (4%, 95% CI 1–10%) with HT had a recommendation change to CT + HT after consideration of the RS, while 18/41 (44%, 95% CI 28–60%) of patients initially recommended CT + HT were subsequently recommended only HT. In the NLR group, 3/19 (16%, 95% CI 3–40%) patients were changed from HT to CT + HT, while 19/48 (40%, 95% CI 26–55%) were changed from CT + HT to HT.ConclusionThere was a significant impact of using the RS in the LR and the NLR group but only 4% of LR patients initially considered for HT had a recommendation change (RC); therefore these patients could forgo ODX testing. A RC was more likely for NLR patients considered for HT. Patients considered for HT + CT have the highest likelihood of a RC based on RS.

Impact of 21-Gene Breast Cancer Assay on Treatment Decision for Patients with T1–T3, N0–N1, Estrogen Receptor-Positive/Human Epidermal Growth Receptor 2-Negative Breast Cancer: Final Results of the Prospective Multicenter ROXANE Study

“…The results of the ROXANE study show that the availability of the RS test for use in clinical practice could lead to a change in adjuvant treatment recommendation in up to 30% of patients for whom the clinicians were initially unsure about treatment recommendation based on classical clinical and pathologic factors. This figure is different from the one of our previous Breast‐DX decision impact study (16% change in treatment decision), conducted in the same Italian region , and more similar to the results of other European cohorts . There are a number of differences among these studies and factors to be considered when interpreting the results.…”

“…As an example, the proportion of N0 patients with grade 3 tumors was higher in the Italian studies (30% in Breast‐DX , 49% in ROXANE) as compared with other European studies (13% in the pooled analysis) . Moreover, most European studies focused on N0 patients, and only few included N1 patients, such as Breast‐DX and ROXANE . Nevertheless, in both Italian studies, the rate of pre‐RS recommendation to HT alone was similar or even higher versus other European studies (52% in Breast‐DX, 48% in ROXANE, 40%–55% in other studies) .…”

“…A number of decision‐impact studies have assessed the rate of change in adjuvant treatment decision associated with the use of the 21‐gene test in European countries. These studies, mostly conducted prior to the availability of the full TAILORx results, generally showed a treatment decision change of around 30% .…”

Summary of head‐to‐head comparisons of patient risk classifications by the 21‐gene Recurrence Score® (RS) assay and other genomic assays for early breast cancer

“…A recently published paper comparing MammaPrint and EndoPredict risk stratification showed a poor correlation between the two tests and noted that following EndoPredict results in the study, a change in therapy decisions in favor of adding chemotherapy to hormone therapy would have occurred in 38% of the patients . Another recent study by the SAKK 26/10 analyzed the decision impact of Oncotype DX testing and reported a change in therapy decision against chemotherapy and in favor of hormone therapy alone in 44% of the patients . A similar recent UK study reported a change against chemotherapy in favor of endocrine therapy alone in 69.2% of patients after the Oncotype DX results were discussed in an interdisciplinary meeting .…”

BCScreen: A gene panel to test for breast carcinogenesis in chemical safety screening

“…Some involve the use of a "seed" or training genes that are already associated with the endpoint or process of interest [52], while others are developed through the manual review of public biomedical and scientific databases. Targeted gene panels have previously been used in a variety of prediction contexts: to identify breast tumor subtype [10], therapeutic response [11], and likelihood of tumor recurrence [37]. Separately, a number of toxicology initiatives have sought to create sentinel or representative gene sets that can serve as markers or predictors of systemic toxicity including Tox21′s S1500+ [31], and the LINCS L1000 list [36,16].…”