A 95-gene signature stratifies recurrence risk of invasive disease in ER-positive, HER2-negative, node-negative breast cancer with intermediate 21-gene signature recurrence scores

Abstract Purpose A subset of patients with intermediate 21-gene signature assay recurrence score may benefit from adjuvant chemoendocrine therapy, but a predictive strategy is needed to identify such patients. The 95-gene signature assay was tested to stratify patients with intermediate RS into high (95GC-H) and low (95GC-L) groups that were associated with invasive recurrence risk.Methods Patients with ER-positive, HER2-negative, node-negative breast cancer and RS 11-25 who underwent definitive surgery and adjuvant endocrine therapy without any cytotoxic agents were included. RNA was extracted from archived formalin-fixed, paraffin-embedded samples, and 95-gene signature was calculated. Results Two hundred six patients had RS of 11-25 (95GC-L, N = 163; 95GC-H, N = 43). In Cox proportional hazards model, 95GC-H was significantly associated with shorter time to recurrence than was 95GC-L (HR 5.94; 95%CI 1.81-19.53; P = 0.005). The correlation between 95-gene signature and 21-gene signature assay scores was not strong (correlation coefficient r = 0.27), which might suggest that 95-gene signature reflects biological characteristics differing from what 21-gene signature shows.Conclusions The 95-gene signature stratifies patients with ER-positive, HER2-negative, node-negative invasive breast cancer and intermediate RS of 11-25 into high and low groups that are associated with recurrence risk of invasive disease. Further retrospective analysis in the prospectively-accrued TAILORx population is warranted to confirm that 95-gene signature can identify patients who would benefit from adjuvant chemoendocrine therapy.

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Cost Effectiveness of Molecular Profiling for Adjuvant Decision Making in Patients With Node-Negative Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2013.54.9931 ◽

2014 ◽

Vol 32 (31) ◽

pp. 3513-3519 ◽

Cited By ~ 17

Author(s):

Julia Bonastre ◽

Sophie Marguet ◽

Beranger Lueza ◽

Stefan Michiels ◽

Suzette Delaloge ◽

...

Keyword(s):

Breast Cancer ◽

Decision Making ◽

Cost Effectiveness ◽

Adjuvant Chemotherapy ◽

Cost Effective ◽

Gene Signature ◽

Node Negative ◽

Node Negative Breast Cancer ◽

Life Years ◽

Er Positive

Purpose To conduct an economic evaluation of the 70-gene signature used to guide adjuvant chemotherapy decision making both in patients with node-negative breast cancer (NNBC) and in the subgroup of estrogen receptor (ER) –positive patients. Patients and Methods We used a mixed approach combining patient-level data from a multicenter validation study of the 70-gene signature (untreated patients) and secondary sources for chemotherapy efficacy, unit costs, and utility values. Three strategies on which to base the decision to administer adjuvant chemotherapy were compared: the 70-gene signature, Adjuvant! Online, and chemotherapy in all patients. In the base-case analysis, costs from the French National Insurance Scheme, life-years (LYs), and quality-adjusted life-years (QALYs) were computed for the three strategies over a 10-year period. Cost-effectiveness acceptability curves using the net monetary benefit were computed, combining bootstrap and probabilistic sensitivity analyses. Results The mean differences in LYs and QALYs were similar between the three strategies. The 70-gene signature strategy was associated with a higher cost, with a mean difference of €2,037 (range, €1,472 to €2,515) compared with Adjuvant! Online and of €657 (95% CI, −€642 to €3,130) compared with systematic chemotherapy. For a €50,000 per QALY willingness-to-pay threshold, the probability of being the most cost-effective strategy was 92% (76% in ER-positive patients) for the Adjuvant! Online strategy, 6% (4% in ER-positive patients) for the systematic chemotherapy strategy, and 2% (20% in ER-positive patients) for the 70-gene strategy. Conclusion Optimizing adjuvant chemotherapy decision making based on the 70-gene signature is unlikely to be cost effective in patients with NNBC.

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A novel 95-gene signature (Curebest 95GC Breast) that predicts recurrence-risk in patients with ER-positive, HER2-negative, node-negative, early-stage primary invasive breast cancer with an intermediate Oncotype DX Recurrence Score.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.542 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 542-542

Author(s):

Takeo Fujii ◽

Hiroko Masuda ◽

Yee Chung Cheng ◽

Fei Yang ◽

Aysegul A. Sahin ◽

...

Keyword(s):

Breast Cancer ◽

Invasive Breast Cancer ◽

Recurrence Score ◽

Recurrence Risk ◽

Gene Signature ◽

Oncotype Dx ◽

Node Negative ◽

Er Positive ◽

Chemoendocrine Therapy ◽

Oncotype Dx Recurrence Score

542 Background: The TAILORx trial demonstrated that adjuvant endocrine and chemoendocrine therapies had similar efficacy in patients with hormone receptor-positive, HER2-negative, node-negative breast cancer with an Oncotype DX recurrence score (RS) of 11-25. However, a predictive strategy is needed to identify patients with intermediate RS who may benefit from adjuvant chemoendocrine therapy. Curebest 95GC Breast (95GC) is a 95-gene signature that can stratify patients into two groups with high (95GC-H) and low (95GC-L) groups to predict the risk of recurrence. Our primary objective was to show that 95GC can classify patients with intermediate RS into binary recurrence risk groups. Methods: Patients with ER-positive, HER2-negative, node-negative invasive breast cancer and RS 11-30 who underwent definitive surgery and adjuvant endocrine therapy were included. RNA was derived from archived formalin-fixed, paraffin-embedded samples, and 95GC was calculated as reported previously. The Fisher exact and Brunner-Munzel tests were used to compare variables between 95GC groups. A Kaplan-Meier estimate with a log-rank test was used for recurrence-free survival (RFS) analysis. Results: The analysis included 178 patients from five institutions. The 5-year RFS rate in patients with RS 18-30 was higher in the 95GC-L group (n = 129, 96.3%) than in the 95GC-H group (n = 49, 90.9%; p = 0.002), which was consistent with results in an independent Japanese population (n = 224; p < 0.001). RFS rates significantly differed between the groups among patients with RS 11-25 as well (95GC-L, 97.4%; 95GC-H, 87.1%; p = 0.001). RFS rates did not differ between patients with RS 18-25 (94.8%) and those with RS 26-30 (93.8%; p = 0.33). Conclusions: 95GC can predict recurrence risk in patients with ER-positive, HER2-negative, node-negative invasive breast cancer and intermediate RS. Further prospective retrospective studies in the TAILORx population are warranted to confirm that 95GC can identify patients who may benefit from adjuvant chemoendocrine therapy.

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