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. 2023 Feb 28;15(5):1529.
doi: 10.3390/cancers15051529.

Impact of the 21-Gene Assay in Patients with High-Clinical Risk ER-Positive and HER2-Negative Early Breast Cancer: Results of the KARMA Dx Study

Antonio Llombart-Cussac  1   2 , Antonio Anton-Torres  3 , Beatriz Rojas  4 , Raquel Andrés  5 , Noelia Martinez  6 , César A Rodríguez  7 , Sara Marin  1 , Teresa Puértolas  3 , Alejandro Falcón González  8 , María Leonor Fernández-Murga  1 , Carlos Hagen  9 , Manuel Ruiz-Borrego  8
Affiliations

Impact of the 21-Gene Assay in Patients with High-Clinical Risk ER-Positive and HER2-Negative Early Breast Cancer: Results of the KARMA Dx Study

Antonio Llombart-Cussac et al. Cancers (Basel). .

Abstract

Background: The 21-gene Oncotype DX Breast Recurrence Score® assay is prognostic and predictive of chemotherapy benefit for patients with estrogen receptor-positive, HER2- early breast cancer (EBC). The KARMA Dx study evaluated the impact of the Recurrence Score® results (RS) on the treatment decision for patients with EBC and high-risk clinicopathological characteristics for whom chemotherapy (CT) was considered.

Methods: Eligible patients with EBC were candidates for the study if CT was considered standard recommendation by local guidelines. Three high-risk EBC cohorts were predefined: (A) pT1-2, pN0/N1mi, and grade 3; (B) pT1-2, pN1, and grades 1-2; and (C) neoadjuvant cT2-3, cN0, and Ki67 ≤ 30%. Treatment recommendations before and after 21-gene testing were registered, as well as treatment received and physicians' confidence levels in their final recommendations.

Results: A total of 219 consecutive patients were included from eight Spanish centers: 30 in cohort A, 158 in cohort B, and 31 in cohort C. Ten patients were excluded from the final analysis as CT was not initially recommended. After 21-gene testing, treatment decisions changed from CT + endocrine therapy (ET) to ET alone for 67% of the whole group. In total, 30% (95% confidence interval [CI] 15% to 49%), 73% (95% CI 65% to 80%), and 76% (95% CI 56% to 90%) of patients ultimately received ET alone in cohorts A, B, and C, respectively. Physicians' confidence in their final recommendations increased in 34% of cases.

Conclusions: Use of the 21-gene test resulted in an overall 67% reduction in CT recommendation in patients considered candidates for CT. Our findings indicate the substantial potential of the 21-gene test to guide CT recommendations in patients with EBC considered to be at high risk of recurrence based on clinicopathological parameters, regardless of nodal status or treatment setting.

Keywords: Oncotype DX Breast Recurrence Score®; Recurrence Score® result; adjuvant; breast cancer; chemotherapy; clinical utility.

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Conflict of interest statement

Llombart-Cussac reported playing a leadership role at Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, and MSD; intellectual property for MedSIR; a consulting role for Lilly, Roche, Pfizer, Novartis, Pierre-Fabre, ExactSciences, Seagen, and GSK; to be part of the speaker bureau for Lilly, AstraZeneca, and MSD; to receive research funding from Pfizer, Roche, Foundation Medicine, ExactSciences, Pierre-Fabre, and Agendia, and travel compensation from Roche, Lilly, Novartis, Pfizer, and AstraZeneca.

Figures

Figure 1
Figure 1
Study flow diagram. CT, chemotherapy; N0, node-negative; N1, node-positive.
Figure 2
Figure 2
Distribution of Recurrence Score groups, by cohort (n = 219). Percentages may not sum to 100% because of rounding. RS, Recurrence Score result.
Figure 3
Figure 3
Change in treatment recommendations after 21-gene testing by cohort (n = 209). Change to omit CT indicates a change from CT + ET → HT in Cohorts A and B, and from CT → ET in Cohort C. CT, chemotherapy; CT + ET, chemotherapy plus endocrine therapy; ET, endocrine therapy alone.
Figure 4
Figure 4
Change in treatment recommendations after 21-gene testing, by cohort and Recurrence Score group (n = 209). Change to omit CT indicates a change from CT + ET to ET in Cohorts A and B, and from CT to ET in Cohort C. CT, chemotherapy; CT + ET, chemotherapy plus hormonal therapy; ET, hormonal therapy alone; RS, Recurrence Score result.
Figure 5
Figure 5
Physicians’ levels of confidence in post-test treatment recommendations for patients with Recurrence Score results (n = 209).
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