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Original Investigation
January 11, 2018

Association of 70-Gene Signature Assay Findings With Physicians’ Treatment Guidance for Patients With Early Breast Cancer Classified as Intermediate Risk by the 21-Gene Assay

Author Affiliations
  • 1Virginia Piper Cancer Center, Minneapolis, Minnesota
  • 2Cardinal Bernardin Cancer Center, Loyola University Stritch School of Medicine, Maywood, Illinois
  • 3Agendia, Inc, Irvine, California
  • 4Aurora Advanced Healthcare, Milwaukee, Wisconsin
  • 5St Clair Hospital, Bethel Park, Pennsylvania
  • 6Roswell Park Cancer Institute, Buffalo, New York
  • 7Nashville Breast Center, Nashville, Tennessee
  • 8Western Maryland Health System Schwab Family Cancer Center, Cumberland, Maryland
  • 9Northern Indiana Cancer Research Consortium, South Bend, Indiana
  • 10Lynchburg Hematology Oncology, Lynchburg, Virginia
  • 11Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, Florida
  • 12Moffitt Cancer Center, Tampa, Florida
JAMA Oncol. 2018;4(1):e173470. doi:10.1001/jamaoncol.2017.3470
Key Points

Question  Are 70-gene signature assay findings associated with physicians’ treatment decisions for patients with intermediate findings on the 21-gene assay?

Findings  In this study of 840 patients with early breast cancer, 282 physicians (33.6%) changed their treatment decision after receiving the 70-gene assay result. Adjuvant chemotherapy was added and removed so that 88% of high-risk patients were recommended to receive chemotherapy and 91% of low-risk patients were recommended no chemotherapy.

Meaning  The 70-gene signature assay provides clinically actionable information, and the findings may be associated with adjuvant therapy decisions.


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.