Patients (pts) with ER+, HER2– early breast cancer (EBC) do not universally benefit from adding adjuvant chemotherapy (CT) to hormonal treatment (HT). The 21-gene Oncotype DX Breast Recurrence Score® (RS) assay is uniquely designed and validated to guide CT treatment decisions in this population.
The primary objective of the KARMA Dx study was to assess the impact of the RS result on treatment recommendations in high-risk patients for whom CT benefit was uncertain. Secondary objective was the evaluation of physicians’ confidence in their recommendation. This study was performed before the recent publication of the TAILORx trial that definitively determined RS cut-points for CT benefit. Eligible EBC pts were ER+, HER2– candidates for CT based on high-risk clinicopathologic features: · Cohort A: grade 3, N0/N1mic · Cohort B: grade 1-2, N1-3, or · Cohort C: cT > 2 cm N0 by imaging (not T4) and planned for neoadjuvant CT Recommendations were captured before and after availability of individual RS results. Primary outcome was the percent change in CT recommendations post- vs. pre-RS results.
Cohort Changes in recommendation Recurrence Score (RS) groups Total n 0-17 18-30 31-100 CT + HT to HT alone 99 (86%) 39 (53%) 2 (10%) 140 (67%) No change 16 (14%) 35 (47%) 18 (90%) 69 (33%) Total n 115 74 20 209 CT + HT to HT alone 5 (56%) 3 (27%) 1 (10%) 9 (30%) No change 4 (44%) 8 (73%) 9 (90%) 21 (70%) Total n 9 11 10 30 CT + HT to HT alone 78 (91%) 31 (54%) 0 109 (73%) No change 8 (9%) 26 (46%) 7 (100%) 41 (27%) Total n 86 57 7 150 CT + HT to HT alone 16 (80%) 5 (83%) 1 (33%) 22 (76%) No change 4 (20%) 1 (17%) 2 (67%) 7 (24%) Total n 20 6 3 29
219 pts with median age of 55 years were recruited in 7 Spanish centers and 209 pts were included in the final analysis. Recommendations changed from CT + HT to HT alone for 67% (140) of patients. The table shows changes in recommendations by cohort and RS group. Considering that 85% of patients had RS 0-25, using these TAILORx cut-points might further affect CT reduction. Physicians’ confidence in their final recommendation increased in 34% of cases.
RS testing resulted in an overall 67% reduction in CT recommendation in pts considered candidates for CT based on clinicopathologic criteria. These results reached 76% for patients in cohort C. The findings of the present study indicate the significant potential of the 21-gene assay to spare CT in high-risk EBC pts.
Hospital Arnau de Vilanova.
Genomic Health Inc.
A. Llombart: Grants/research support: Genomic Health Inc.; Stock shareholder: MedSIR. All other authors have declared no conflicts of interest.