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

• Published in: Cancers 2023-02, Vol.15 (5), p.1529
• Main Authors: Llombart-Cussac, Antonio, Anton-Torres, Antonio, Rojas, Beatriz, Andrés, Raquel, Martinez, Noelia, Rodríguez, César A, Marin, Sara, Puértolas, Teresa, González, Alejandro Falcón, Fernández-Murga, María Leonor, Hagen, Carlos, Ruiz-Borrego, Manuel
• Format: Article
• Language: English
• Subjects: Biochemical assays; Breast cancer; Cancer; Cancer therapies; Chemotherapy; Consent; Endocrine therapy; ErbB-2 protein; Estrogen receptors; Genetic screening; Lymphatic system; Medical prognosis; Methods; Patient outcomes; Patients; Physicians; Surgery
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers15051529

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. 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. 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. 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.