Abstract
IMPORTANCE: Among patients who undergo the 21-gene assay (21-GA), 39% to 67% receive an intermediate risk result and may receive ambiguous treatment guidance. The 70-gene signature assay (70-GS) may be associated with physicians' treatment decisions in this population with early breast cancer. OBJECTIVE: To determine whether 70-GS findings are associated with physicians' decisions about adjuvant treatment and confidence in their recommendations and to evaluate the dichotomous (high- vs low-risk) and continuous distribution of 70-GS indices among this group of patients with intermediate risk. DESIGN, SETTING, AND PARTICIPANTS: The Prospective Study of MammaPrint in Breast Cancer Patients With an Intermediate Recurrence Score (PROMIS trial) was an impact study conducted from May 20, 2012, through December 31, 2015, that enrolled 840 patients with early-stage breast cancer and a 21-gene assay recurrence score of 18 to 30. Patients were treated in 58 US institutions. INTERVENTIONS: The 70-GS result was given to physicians before adjuvant treatment. MAIN OUTCOMES AND MEASURES: Change in physician treatment decision before vs after receiving the 70-GS result. With a treatment change of greater than 20%, the odds ratio (OR) was applied. RESULTS: Among the 840 patients who underwent 70-GS classification (mean age, 59 years; range, 27-93 years), 374 (44.5%) had a low-risk and 466 (55.5%) had a high-risk result. The distribution of 70-GS indices did not correlate with recurrence score within the 21-GA intermediate range, with 70-GS low- and high-risk patients observed at every recurrence score. A significant change in adjuvant treatment was associated with receiving the 70-GS classifications with an OR of 0.64 (95% CI, 0.50-0.82; McNemar test, P < .001) for all patients. Among the low-risk patients, 108 of 374 (28.9%) had chemotherapy removed from their treatment recommendation; among the high-risk patients, 171 of 466 (36.7%) had chemotherapy added. Results of the 70-GS were associated with the physician's adjuvant treatment recommendation; 409 high-risk patients (87.8%) were recommended to receive adjuvant chemotherapy, and 339 low-risk patients (90.6%) were recommended no chemotherapy. Physicians reported having greater confidence in their treatment recommendation in 660 cases (78.6%) based on 70-GS results. CONCLUSIONS AND RELEVANCE: The 70-GS provides clinically actionable information regarding patients classified as intermediate risk by the 21-GA and was associated with a change in treatment decision in 282 of these patients (33.6%). Chemotherapy was added or withheld by the treating physician based on the results of the 70-GS test. Physicians reported more confidence with their treatment recommendation after receiving 70-GS results.